WEBVTT 00:00:08.183 --> 00:00:08.566 We're going to 00:00:08.566 --> 00:00:11.566 continue talking about leukemias, 00:00:11.866 --> 00:00:15.300 Alall, our mature B-cell mature T cell. 00:00:15.300 --> 00:00:18.000 And in cell leukemias. 00:00:18.000 --> 00:00:18.350 All right. 00:00:18.350 --> 00:00:21.750 So today we're going to talk about our acute lymphocytic 00:00:21.750 --> 00:00:24.750 lymphoblastic leukemia which is AML. 00:00:25.066 --> 00:00:28.350 Our mature B-cell leukemias mature T. 00:00:28.350 --> 00:00:31.350 And in case of leukemias. 00:00:32.716 --> 00:00:34.500 Al is acute 00:00:34.500 --> 00:00:37.500 lymphocytic or lymphoblastic leukemia. 00:00:38.600 --> 00:00:41.600 Al is the make 00:00:41.900 --> 00:00:44.916 ALK makes up one third to one 00:00:44.916 --> 00:00:47.916 half of all childhood malignancies. 00:00:48.016 --> 00:00:51.683 It's the second most common cause of death in the age range. 00:00:51.683 --> 00:00:54.300 Between 1 and 15. 00:00:54.300 --> 00:00:57.350 ALK is seen in 80 00:00:57.350 --> 00:01:00.533 to 90% of pediatric leukemias. 00:01:01.133 --> 00:01:05.866 The peak incidence age is between 2 and 6 years of age, 00:01:06.383 --> 00:01:09.383 and dry bone marrow taps happen frequently. 00:01:10.883 --> 00:01:14.183 For Aiello, the Who classifications 00:01:14.900 --> 00:01:18.866 are acute lymphoblastic leukemia or lymphoma, 00:01:19.616 --> 00:01:22.616 which includes precursor B 00:01:22.733 --> 00:01:26.116 acute lymphoblastic leukemia or lymphoma. 00:01:26.816 --> 00:01:29.816 There are several different cytogenetics subtypes 00:01:30.300 --> 00:01:35.100 the translocation 1221, which is Tel, AML, or ETB 00:01:36.350 --> 00:01:40.100 or ETB six ranks one is 00:01:41.000 --> 00:01:44.900 unusual in that it is cryptic by chromosomes, 00:01:45.316 --> 00:01:49.400 because the size of the pieces are about the same 00:01:49.816 --> 00:01:52.816 and the banding pattern is very similar. 00:01:53.183 --> 00:01:55.600 I can't see it by chromosomes. 00:01:55.600 --> 00:01:58.616 You've got to do to detect it by fish. 00:01:59.966 --> 00:02:02.966 A translocation 119, 00:02:03.600 --> 00:02:05.966 which results in PBKs one 00:02:05.966 --> 00:02:08.966 and E2, a translocation, 00:02:09.350 --> 00:02:13.666 a translocation 922 that we saw in CML, 00:02:13.850 --> 00:02:19.316 which is between ABL and BCR, and then variant partners 00:02:19.316 --> 00:02:23.933 with chromosome 11 Q23, which is KMT tumor. 00:02:24.616 --> 00:02:30.500 So the v T v 11 is variant for translocation 00:02:31.466 --> 00:02:33.983 Aso precursor T 00:02:33.983 --> 00:02:37.433 acute lymphoblastic leukemia or lymphoma. 00:02:37.916 --> 00:02:41.100 Bearcats leukemia lymphoma and a bi 00:02:41.100 --> 00:02:44.100 phenotypic acute leukemia. 00:02:44.700 --> 00:02:47.033 Acute lymphoblastic leukemia 00:02:47.033 --> 00:02:51.233 generally is a precursor B-cell. 00:02:52.166 --> 00:02:56.700 It's a primary disease of childhood 75% 00:02:56.700 --> 00:03:00.350 of all patients and during the age of six 00:03:00.616 --> 00:03:03.683 are going to have this precursor B-cell. 00:03:04.250 --> 00:03:07.100 It makes up 80 to 85% of 00:03:07.100 --> 00:03:10.100 pediatric Aiello cases. 00:03:10.283 --> 00:03:13.283 The good news about it is that the childhood 00:03:13.400 --> 00:03:17.150 overall cure rates are over 90%. 00:03:18.000 --> 00:03:19.016 T-cell 00:03:20.250 --> 00:03:22.216 acute lymphoblastic leukemia 00:03:22.216 --> 00:03:25.633 is only 15% of the childhood leukemias, 00:03:26.150 --> 00:03:29.750 and about 25% of adult ALK cases. 00:03:31.766 --> 00:03:33.300 For abnormalities 00:03:33.300 --> 00:03:36.833 that we see in the B-cell alpha childhood 00:03:36.833 --> 00:03:39.833 again, the translocation 1221 00:03:40.200 --> 00:03:43.800 between Tel, AML or ETV six ranks one. 00:03:44.516 --> 00:03:48.916 That's going to be present in about 15 to 35% of the cases. 00:03:48.916 --> 00:03:52.766 It's one of the most common rearrangements that we see. 00:03:53.250 --> 00:03:56.250 It is a good prognostic indicator. 00:03:56.600 --> 00:03:59.366 But again it is cryptic by chromosomes 00:03:59.366 --> 00:04:02.366 and must be detected by fish. 00:04:03.000 --> 00:04:05.700 The translocation 411 is one that 00:04:05.700 --> 00:04:09.266 we don't see very often, but it's a very important one. 00:04:09.683 --> 00:04:12.683 It's only seen in 2 to 3% of the cases. 00:04:13.066 --> 00:04:17.033 It's most common in children under the age of 12 months, 00:04:17.033 --> 00:04:21.450 but it does carry a very poor prognostic indicator. 00:04:22.400 --> 00:04:25.366 A high hyper diploid is something that we see 00:04:25.366 --> 00:04:29.033 frequently for B-cell alpha in childhood. 00:04:29.600 --> 00:04:34.950 It's a simultaneous gain of multiple chromosomes in one cell division. 00:04:35.516 --> 00:04:38.516 And it is a very good prognostic indicator. 00:04:39.116 --> 00:04:41.033 The gains are nonrandom. 00:04:41.033 --> 00:04:44.633 And they're going to include gain of four 00:04:45.083 --> 00:04:48.350 six 1014 00:04:48.566 --> 00:04:52.550 1718, 21. 00:04:52.950 --> 00:04:55.950 And your sex chromosome from 00:04:57.500 --> 00:05:01.166 and your sex chromosome of chromosome X. 00:05:02.450 --> 00:05:05.250 Interestingly, for the chromosome 00:05:05.250 --> 00:05:11.350 21, about 70% of the cases we actually see two or so me 00:05:11.366 --> 00:05:15.683 or four copies of 21, the remaining 30 cases, 00:05:15.683 --> 00:05:18.683 we see the three copies. 00:05:19.850 --> 00:05:22.250 We do see some structural alterations. 00:05:22.250 --> 00:05:26.933 Also, we're going to see things that cause partial duplication of one cue. 00:05:27.450 --> 00:05:31.283 So again, that Der one seven that we talked about previously, 00:05:31.666 --> 00:05:34.666 that results in a gain of one q 00:05:34.666 --> 00:05:37.066 translocation, 119 00:05:38.750 --> 00:05:39.500 we either 00:05:39.500 --> 00:05:45.016 see that as the balanced translocation where we have a derivative chromosome one 00:05:45.500 --> 00:05:48.383 and a derivative chromosome 19, 00:05:48.383 --> 00:05:51.416 or sometimes we see it with two normal ones. 00:05:51.833 --> 00:05:56.183 And the derivative 19, that again results in a duplication 00:05:56.183 --> 00:06:00.500 of 1QA deleted chromosome six q 00:06:01.500 --> 00:06:03.533 translocation 922. 00:06:03.533 --> 00:06:07.283 This is the same translocation we talked about with CML. 00:06:08.516 --> 00:06:11.516 A deleted £0.09 00:06:11.566 --> 00:06:14.783 rearrangements of 11 Q that involve 00:06:14.783 --> 00:06:18.533 KMT two A at 11 Q23 00:06:19.500 --> 00:06:22.316 deletions of £0.12, 00:06:22.316 --> 00:06:24.716 and then an ISIL 17 Q 00:06:24.716 --> 00:06:29.100 that results in a loss of £0.17, which has our tumor 00:06:29.100 --> 00:06:32.100 suppressor gene Tp53 on there. 00:06:34.216 --> 00:06:37.883 We do see different platy levels for Al. 00:06:38.000 --> 00:06:41.000 And so they can be a high hyper diploid, 00:06:41.900 --> 00:06:44.033 which is the most common 00:06:44.033 --> 00:06:47.033 in 20 to 25% of the cases. 00:06:47.116 --> 00:06:51.750 For those, we're going to have between 51 to 65 chromosomes. 00:06:52.433 --> 00:06:57.533 We can have a near haploid which is 22 to 29 chromosomes. 00:06:58.283 --> 00:07:01.500 That's not very frequently only 00:07:01.500 --> 00:07:04.700 about 5% of the cases, but it is very important. 00:07:06.450 --> 00:07:07.816 A low hypo 00:07:07.816 --> 00:07:11.216 diploid of 31 to 39 chromosomes, 00:07:11.666 --> 00:07:15.716 near triploid of 66 to 79 chromosomes 00:07:16.100 --> 00:07:20.100 near tetra polarity of 84 to 100 chromosomes, 00:07:20.550 --> 00:07:24.916 and a low hyper diploid of 47 to 49 chromosomes. 00:07:26.783 --> 00:07:31.750 We can also see what they call hypo diploid, which is a loss of 1 00:07:31.750 --> 00:07:36.466 or 2 chromosomes, however, that's normally seen with trisomy five. 00:07:36.466 --> 00:07:39.466 So I have a loss of 1 or 2 chromosomes. 00:07:39.466 --> 00:07:42.466 But I have three chromosome five. 00:07:43.816 --> 00:07:48.266 I've given you an example of a high hyper diploid where we have 00:07:48.266 --> 00:07:53.116 a gain of chromosome 4692 00:07:53.116 --> 00:07:56.450 copies, two extra copies of chromosome ten, 00:07:57.166 --> 00:08:00.266 two extra copies of chromosome 18, 00:08:01.200 --> 00:08:04.200 two extra copies of chromosome 21, 00:08:04.966 --> 00:08:09.166 an extra X and an extra Y on the bottom. 00:08:09.166 --> 00:08:12.866 Karyotype is an example of a near haploid. 00:08:13.966 --> 00:08:15.233 The near haploid 00:08:15.233 --> 00:08:20.216 is close to our haploid number of 23, but the chromosomes 00:08:20.216 --> 00:08:24.716 that remain as dicer me two copies are nonrandom. 00:08:26.483 --> 00:08:28.883 Here is a hyper diploid karyotype. 00:08:28.883 --> 00:08:31.883 For alpha. Let's cut 55 chromosomes. 00:08:32.450 --> 00:08:37.950 I have plus four plus six plus ten plus 14. 00:08:38.566 --> 00:08:40.550 I have plus 17. 00:08:40.550 --> 00:08:46.733 But one of my chromosome 17 has additional material on the end of the long arm 00:08:47.450 --> 00:08:51.816 plus 18 plus a gain of two chromosome 21 00:08:52.350 --> 00:08:55.350 and plus my ex X chromosome. 00:08:57.283 --> 00:08:59.333 Adult bowel is less 00:08:59.333 --> 00:09:02.333 characterized than pediatric aiello. 00:09:02.366 --> 00:09:04.950 About 25% of the cases 00:09:04.950 --> 00:09:08.033 are going to have the translocation 922 00:09:08.516 --> 00:09:12.316 between BCR and able that we've already talked about 00:09:13.350 --> 00:09:18.900 11 to 2 three rearrangements of KMT two are much more common 00:09:18.900 --> 00:09:23.000 in adult below than they are in childhood. 00:09:23.300 --> 00:09:27.683 Bowel rearrangements involving C, MC 00:09:27.683 --> 00:09:33.383 and AQ 24 are also seen in adult bowel, 00:09:34.316 --> 00:09:38.116 the hyper diploid of more than 51 chromosomes 00:09:38.116 --> 00:09:43.316 that we just talked about that was seen frequently in children is rarely seen 00:09:43.316 --> 00:09:48.450 in adult bowel, so much less frequently than we saw in children. 00:09:49.466 --> 00:09:50.716 Then the tail 00:09:50.716 --> 00:09:55.216 AML or translocation 1221 childhood alteration 00:09:55.616 --> 00:09:58.616 that we couldn't detect by chromosomes, 00:09:58.616 --> 00:10:01.733 luckily, is not seen in Buffalo. 00:10:02.250 --> 00:10:05.250 It's also not generally fish for 00:10:05.416 --> 00:10:08.966 because it's not something that it just doesn't occur. 00:10:09.600 --> 00:10:13.850 I've given you some AQ two for Cmac variants. 00:10:14.483 --> 00:10:16.916 Translocation 814. 00:10:16.916 --> 00:10:19.916 So it's the end of chromosome eight 00:10:20.100 --> 00:10:24.650 and the end of chromosome 14 that translocate. 00:10:25.466 --> 00:10:27.566 And then 822. 00:10:27.566 --> 00:10:30.766 So again here is my abnormal 22 00:10:31.316 --> 00:10:35.533 and my abnormal chromosome eight T cell 00:10:35.550 --> 00:10:38.716 alpha is coming from lymph 00:10:38.716 --> 00:10:41.716 oblast committed to the T cell lineage 00:10:42.150 --> 00:10:44.866 I can have precursor to yellow 00:10:44.866 --> 00:10:47.866 which is also called pretty Alo. 00:10:48.383 --> 00:10:52.733 That makes up about 15% of my childhood ALC cases 00:10:53.216 --> 00:10:57.016 and about 25% of my adult ALK cases. 00:10:57.533 --> 00:11:00.683 It is more common in adolescent males. 00:11:01.466 --> 00:11:03.766 I can also have a precursor 00:11:03.766 --> 00:11:07.283 T lymphoblastic leukemia or lymphoma, 00:11:07.916 --> 00:11:11.000 also called a pretty LBL. 00:11:11.866 --> 00:11:16.200 It's about 85 to 90% of my LBL cases. 00:11:16.200 --> 00:11:19.400 And again, it's more common in adolescent males. 00:11:20.933 --> 00:11:24.533 About 30% of T cell ALK cases 00:11:24.533 --> 00:11:28.616 will have a deletion of the short arm of chromosome nine. 00:11:28.616 --> 00:11:31.666 So £0.09 results in a loss 00:11:31.666 --> 00:11:34.666 of a gene called CDK into a. 00:11:35.600 --> 00:11:38.933 About 33% will have translocations 00:11:38.933 --> 00:11:42.466 that involve my T cell receptor loci. 00:11:43.050 --> 00:11:46.050 So I have T cell receptor loci 00:11:46.200 --> 00:11:49.200 that map to 14 Q 11.2 00:11:49.200 --> 00:11:52.200 just below the centromere on 14. 00:11:52.216 --> 00:11:56.816 And I also have one that maps to 7Q35 00:11:57.300 --> 00:12:01.316 and one that maps to 7P1415. 00:12:02.333 --> 00:12:05.550 Some of the partner chromosomes that are 00:12:06.566 --> 00:12:09.750 translocated with these T cell receptor loci 00:12:10.216 --> 00:12:13.350 are seen MC on eight, two, 24.1 00:12:14.116 --> 00:12:17.116 to L1 or tau one on one, p 00:12:17.116 --> 00:12:21.683 three to RB, t in one on 11, 00:12:21.683 --> 00:12:26.716 P15, RB ten, two on 11, P13, 00:12:27.200 --> 00:12:29.716 and Hox 11 on ten, Q two 00:12:29.716 --> 00:12:32.966 for giving you a couple different. 00:12:32.966 --> 00:12:35.966 So here is a translocation 710. 00:12:36.350 --> 00:12:38.816 You can see seven is too short. 00:12:38.816 --> 00:12:41.816 That extra material has gone back to ten. 00:12:42.350 --> 00:12:45.600 The very little material of ten went to seven. 00:12:46.283 --> 00:12:49.616 Here is a translocation 1114. 00:12:49.616 --> 00:12:53.483 So you can see that most of my chromosome 14 arm 00:12:54.016 --> 00:12:57.016 is on the short arm of chromosome 11. 00:12:57.683 --> 00:13:00.766 Not much of 11 went back to my 14. 00:13:01.466 --> 00:13:04.316 Here's the translocation 814 again 00:13:05.483 --> 00:13:07.666 at translocation 714. 00:13:07.666 --> 00:13:11.183 Now this one is interesting because it involves 00:13:11.600 --> 00:13:15.300 a translocation between two T cell receptor loci. 00:13:15.716 --> 00:13:21.083 So my T cell receptor loci at 7P15. 00:13:21.533 --> 00:13:25.250 And then my T cell receptor loci on 14 Q 00:13:26.850 --> 00:13:29.416 a translocation 1416 00:13:29.416 --> 00:13:32.416 and a translocation 1418. 00:13:34.200 --> 00:13:37.100 Mature B cell leukemias. 00:13:37.100 --> 00:13:40.816 Mature B cell leukemias are going to include CLL. 00:13:42.050 --> 00:13:45.166 CLL is chronic lymphocytic leukemia. 00:13:45.683 --> 00:13:48.950 When CML is lymphoma, it's called 00:13:48.950 --> 00:13:52.283 small lymphocytic lymphoma or slow. 00:13:52.283 --> 00:13:56.366 So CL and SL are the same things. 00:13:56.750 --> 00:14:00.150 The difference is that CLL is a leukemia. 00:14:00.150 --> 00:14:04.400 So in the blood and bone marrow SL is a lymphoma 00:14:04.666 --> 00:14:07.433 in your lymphatic tissue 00:14:07.433 --> 00:14:13.166 a B cell pro lymphoblastic lymphoma or b LBL 00:14:13.816 --> 00:14:18.083 Wahlstrom S macro globular anemia and hairy cell leukemia, 00:14:19.016 --> 00:14:22.550 part of the mature B cell neoplasms also include 00:14:22.550 --> 00:14:26.266 plasma cell disorders that we'll talk about in a few minutes. 00:14:27.600 --> 00:14:29.200 So CL and 00:14:29.200 --> 00:14:33.683 SL again are the same disease just different locations. 00:14:34.216 --> 00:14:37.916 It's the most common adult leukemia in the Western world. 00:14:39.450 --> 00:14:42.616 It's predominantly a disease of older individuals. 00:14:42.616 --> 00:14:45.950 Most of the individuals are greater than the age of 50 00:14:45.950 --> 00:14:52.166 at the time of diagnosis, about 25% of the patients are asymptomatic, 00:14:52.500 --> 00:14:55.550 and it's diagnosed on a routine CBC, 00:14:55.550 --> 00:14:59.066 something similar that we saw with MDS. 00:14:59.700 --> 00:15:02.516 The prognosis is affected by the presence 00:15:02.516 --> 00:15:05.516 or absence of a mutation in IGA, 00:15:06.116 --> 00:15:11.250 and it's a mutation positive CL cases that have a better prognosis 00:15:11.666 --> 00:15:14.550 than the mutation negative cases, which is something 00:15:14.550 --> 00:15:17.550 that we wouldn't have expected 00:15:17.750 --> 00:15:20.250 for recurring alterations 00:15:20.250 --> 00:15:24.266 for CL and slow recurring alterations. 00:15:24.866 --> 00:15:30.116 The abnormalities are very important in prognostic indicators 00:15:30.650 --> 00:15:34.133 and are used in the diagnosis and treatment of CL, 00:15:34.133 --> 00:15:37.650 not all patients with CL will get treatment. 00:15:37.650 --> 00:15:41.600 A lot of times the treatment is just monitoring of the disease. 00:15:42.233 --> 00:15:46.316 So what alterations they have is very important. 00:15:46.966 --> 00:15:51.383 About 80% of CL cases are abnormal by fish. 00:15:51.950 --> 00:15:55.766 Trisomy 12 is one of the things that's commonly seen 00:15:56.100 --> 00:15:58.850 seen in about 20% of the cases. 00:15:58.850 --> 00:16:03.100 And it's generally seen with an annotated IGD gene. 00:16:03.116 --> 00:16:05.400 So it's an intermediate prognosis. 00:16:07.966 --> 00:16:09.600 A deletion of chromosome 00:16:09.600 --> 00:16:13.216 13 is seen in about 50% of the cases. 00:16:13.650 --> 00:16:18.416 However it's frequently seen with mutated IgG genes. 00:16:18.800 --> 00:16:23.183 So with the mutated IGA and only the deleted 00:16:23.183 --> 00:16:26.183 13, that's a good prognosis. 00:16:26.516 --> 00:16:30.150 About 20% of patients will have a deleted 11. 00:16:30.150 --> 00:16:34.883 Q it involves a deletion of the ATM locus 00:16:34.883 --> 00:16:39.200 and that is a important tumor suppressor gene. 00:16:39.200 --> 00:16:42.200 So it's associated with a poor survival. 00:16:42.683 --> 00:16:48.050 Deletions of chromosome £0.17 are seen in about 10%. 00:16:48.050 --> 00:16:52.500 Again that includes our tumor suppressor gene Tp53. 00:16:52.500 --> 00:16:55.500 So it's associated with a poor survival. 00:16:55.550 --> 00:16:58.550 And also deletions in chromosome six 00:16:59.116 --> 00:17:02.416 is seen in about 5% of the patients. 00:17:02.416 --> 00:17:05.416 And it's also a poor prognostic indicator. 00:17:07.733 --> 00:17:11.566 Some rare mature B-cell neoplasms that we see 00:17:11.816 --> 00:17:17.450 with recurring alterations are B-cell Pro lymphocytic leukemia. 00:17:17.450 --> 00:17:19.300 It's about 1% alone. 00:17:20.266 --> 00:17:21.000 It's about 00:17:21.000 --> 00:17:24.833 1% of lymphocytic leukemia is IgG. 00:17:25.250 --> 00:17:28.700 Rearrangements at 14 to 3 two 00:17:28.883 --> 00:17:32.083 is seen in about 20% of the abnormal cases. 00:17:32.700 --> 00:17:37.550 And loss of Tp53 on £0.17 00:17:37.883 --> 00:17:41.416 is seen in about 53% of the abnormal cases. 00:17:42.200 --> 00:17:47.033 The IT rearrangements are not a bad prognostic indicator. 00:17:47.033 --> 00:17:50.616 But again, £0.17 loss of £0.17 00:17:50.633 --> 00:17:53.633 is always a poor prognostic indicator. 00:17:54.200 --> 00:17:57.200 Splenic marginal zone lymphomas 00:17:57.916 --> 00:18:01.666 make up less than 1% of lymphoid neoplasms. 00:18:02.333 --> 00:18:05.416 Generally we're going to see rearrangements involving 00:18:05.416 --> 00:18:08.416 loss of part of seven Q. 00:18:08.450 --> 00:18:12.350 About 40% of those are going to be abnormal cases. 00:18:12.916 --> 00:18:18.050 Hairy cell leukemia is about 2% of our lymphoid leukemias. 00:18:18.450 --> 00:18:21.583 There aren't any specific abnormalities described 00:18:21.583 --> 00:18:25.650 with that disease for our plasma cell disorders. 00:18:25.650 --> 00:18:27.233 The first one we're going to talk about 00:18:27.233 --> 00:18:31.250 is monoclonal gamma APC of undetermined significance. 00:18:31.616 --> 00:18:33.716 It's also called mGUS. 00:18:33.716 --> 00:18:36.716 There has to be less than 10% blast. 00:18:36.916 --> 00:18:40.733 It's usually not treated as the patients are asymptomatic. 00:18:41.216 --> 00:18:44.550 So it is something that they'll follow but not treat at that time. 00:18:45.083 --> 00:18:47.900 It does result in decreased serum 00:18:47.900 --> 00:18:51.683 IgG, IGA and IgG antibodies. 00:18:52.883 --> 00:18:55.883 Wahlstrom macro globulin, Amia 00:18:56.250 --> 00:18:58.250 is also sometimes called 00:18:58.250 --> 00:19:01.066 lymphoid plasma Citic leukemia. 00:19:01.066 --> 00:19:05.300 It's a cancer of the plasma cells and the B lymphocytes. 00:19:05.300 --> 00:19:08.450 So it kind of crosses into both areas. 00:19:09.150 --> 00:19:13.883 You'll have an absence of bone involvement or ostia lytic lesions. 00:19:14.483 --> 00:19:19.666 You do have a serum monoclonal protein that can be picked up by GM 00:19:20.400 --> 00:19:23.033 lymphocyte ptosis with atypical, 00:19:23.033 --> 00:19:26.400 usually immature, plasma cycloid features. 00:19:27.016 --> 00:19:31.400 It's about 1.5% of all nodal lymphomas. 00:19:32.183 --> 00:19:35.183 Pax five, which is on £0.09 00:19:35.716 --> 00:19:39.950 rearrangements, are seen in about 50% of the cases. 00:19:40.400 --> 00:19:43.700 Also, translocations with IgG at 14, 00:19:43.700 --> 00:19:48.016 Q32, at translocation 1118, 00:19:48.016 --> 00:19:51.766 and deletions of chromosome six are also frequently seen. 00:19:53.250 --> 00:19:56.783 Some of the other plasma cell disorders are isolated 00:19:56.783 --> 00:19:59.266 plasma side tumor of the bone. 00:19:59.266 --> 00:20:02.666 Those are generally an isolated lytic lesion 00:20:02.666 --> 00:20:08.400 of the bone, often asymptomatic, and we can also have extra medullary 00:20:08.400 --> 00:20:14.300 plasma side tumor, which is an isolated plasma cell tumor of the soft tissue. 00:20:15.766 --> 00:20:17.850 Our biggest plasma cell disorder, 00:20:17.850 --> 00:20:20.850 though, is multiple myeloma. 00:20:21.616 --> 00:20:25.100 It's a multi focal plasma cell neoplasm. 00:20:25.100 --> 00:20:28.733 You're going to have the serum monoclonal protein AGM. 00:20:29.366 --> 00:20:33.383 It causes skeletal destruction through ostia lytic lesions 00:20:33.750 --> 00:20:36.683 that will end up resulting in fractures. 00:20:36.683 --> 00:20:39.233 It's a systemic malignancy. 00:20:39.233 --> 00:20:42.083 The peak incidence for multiple myeloma 00:20:42.083 --> 00:20:45.083 is between 50 to 60 years old. 00:20:45.350 --> 00:20:48.350 It is treatable, but it is rarely curable. 00:20:48.616 --> 00:20:52.766 And the disease spectrum can go all the way from indolent 00:20:53.366 --> 00:20:55.816 to very aggressive side. 00:20:55.816 --> 00:21:00.766 The genetic analysis is limited by low proliferation of the plasma cells. 00:21:01.500 --> 00:21:03.866 For it to be multiple myeloma, 00:21:03.866 --> 00:21:06.866 you've got to have more than 10% blast. 00:21:07.883 --> 00:21:10.766 But the concentration 00:21:10.766 --> 00:21:12.800 of cd38 positive 00:21:12.800 --> 00:21:16.500 plasma cells helps increase the abnormality rate. 00:21:16.500 --> 00:21:18.800 So one of the things that we do 00:21:18.800 --> 00:21:22.133 is we'll take an adequate of the bone marrow that we receive, 00:21:22.816 --> 00:21:26.866 and we'll try to concentrate it for the plasma cells. 00:21:27.300 --> 00:21:29.816 We use that for our fish set up. 00:21:29.816 --> 00:21:34.016 It would be great to use it for our culture set up for chromosomes. 00:21:34.583 --> 00:21:37.466 Unfortunately, we just don't get enough bone marrow. 00:21:39.016 --> 00:21:40.650 About 20 to 00:21:40.650 --> 00:21:44.633 60% of abnormalities will be detected in new cases. 00:21:44.633 --> 00:21:50.783 The mean is generally between 30 to 40%, but again 20 to 60% 00:21:51.266 --> 00:21:54.416 depending on the study that you look at. 00:21:55.166 --> 00:21:59.566 Part of that has to do with how high 00:21:59.566 --> 00:22:03.233 the plasma cell percent is in the patient being tested. 00:22:04.133 --> 00:22:08.750 About 60 to 70% of patients with progressive disease 00:22:09.166 --> 00:22:13.350 will have recurrent abnormalities, and this makes sense. 00:22:13.350 --> 00:22:16.516 With progressive disease, the patients should have 00:22:16.516 --> 00:22:19.516 a higher blast count. 00:22:19.800 --> 00:22:21.266 Recurring alterations 00:22:21.266 --> 00:22:24.266 that we see in multiple myeloma. 00:22:24.650 --> 00:22:27.316 The most common is a very complex 00:22:27.316 --> 00:22:30.566 karyotype with multiple gains and losses. 00:22:30.566 --> 00:22:35.700 So for common gains we see trisomy three, five, 00:22:35.700 --> 00:22:39.833 seven, nine, 11, 15 and 19. 00:22:40.016 --> 00:22:43.650 So our odd chromosomes for losses 00:22:43.650 --> 00:22:48.783 we tend to see loss of eight 1314 and X. 00:22:49.400 --> 00:22:51.950 Now for chromosome 13 it can be 00:22:51.950 --> 00:22:56.416 monism or the deleted 13 view that is seen in 00:22:56.416 --> 00:23:00.150 15 to 40% of newly diagnosed cases. 00:23:00.900 --> 00:23:04.216 Some recurrent structural abnormalities that we see 00:23:04.883 --> 00:23:08.416 involve chromosomes one, 11 and 14. 00:23:08.850 --> 00:23:13.816 I've given you an example of the translocation 1114, which is very common 00:23:14.850 --> 00:23:16.616 a loss or deletion of 00:23:16.616 --> 00:23:20.150 chromosome 17, again, of Tp53 00:23:20.550 --> 00:23:23.966 seen in about 25% of abnormal cases. 00:23:24.766 --> 00:23:27.233 The deletion of chromosome seven Q 00:23:27.233 --> 00:23:31.500 has been associated with poor drug resistance, 00:23:32.266 --> 00:23:35.266 and the deletion or monism 00:23:35.266 --> 00:23:39.800 13 and deletion of £0.17 are poor. 00:23:39.800 --> 00:23:42.800 Prognostic indicators. 00:23:43.316 --> 00:23:45.566 Here's an example of a hyper diploid 00:23:45.566 --> 00:23:48.566 karyotype seen in multiple myeloma. 00:23:48.750 --> 00:23:54.800 So I have trisomy 357 11. 00:23:55.400 --> 00:23:59.966 I have additional material on my short 00:23:59.966 --> 00:24:05.100 arm of chromosome 12 plus 15 plus 15. 00:24:05.100 --> 00:24:09.716 So two extra copies of my chromosome 15 00:24:10.250 --> 00:24:13.250 plus 19 and plus 21. 00:24:13.666 --> 00:24:15.866 Unlike AML generally 00:24:15.866 --> 00:24:18.966 we just see trisomy 21 and not Tetris. 00:24:18.983 --> 00:24:21.950 On May 21st. 00:24:21.950 --> 00:24:23.116 Some other mature 00:24:23.116 --> 00:24:26.366 B-cell diseases are lymphomas. 00:24:26.550 --> 00:24:31.066 So we have Hodgkin lymphoma and non-Hodgkin lymphoma. 00:24:31.200 --> 00:24:36.416 The non-Hodgkin lymphoma cases that we're going to talk about are Malt lymphomas, 00:24:36.766 --> 00:24:41.700 which are B-cell lymphoma of mucosa associated lymphoid tissues, 00:24:42.233 --> 00:24:44.816 marginal zone lymphomas, follicular 00:24:44.816 --> 00:24:47.816 lymphomas, mantle cell lymphomas. 00:24:47.966 --> 00:24:49.216 Bearcat lymphoma. 00:24:49.216 --> 00:24:54.200 Leukemias are large B-cell lymphoma which can be diffuse, 00:24:54.750 --> 00:24:57.950 thymic, or mediastinum intravascular 00:24:58.283 --> 00:25:01.133 or primary effusion lymphomas. 00:25:01.133 --> 00:25:05.483 Then we also have some B cell proliferation of uncertain malignant 00:25:05.483 --> 00:25:06.566 potential. 00:25:06.566 --> 00:25:10.650 Those are broken down into lymphoma Toid granule 00:25:11.900 --> 00:25:14.900 lymphoma, Toid granule mitosis 00:25:14.966 --> 00:25:18.800 and post-transplant lymphoid proliferative disorder 00:25:19.850 --> 00:25:23.333 are marked lymphoma or extra marginal zone 00:25:23.333 --> 00:25:27.466 lymphoma of mucosal associated lymphoid tissue 00:25:28.516 --> 00:25:31.700 is 7 to 8% of our B-cell lymphoma. 00:25:31.916 --> 00:25:34.883 About 50% of our primary gastric 00:25:34.883 --> 00:25:37.883 lymphomas are Malt lymphomas, though 00:25:38.066 --> 00:25:40.516 trisomy three is something that we see 00:25:40.516 --> 00:25:43.516 in about 60% of the cases. 00:25:43.550 --> 00:25:46.700 Also, this translocation 1118 00:25:47.666 --> 00:25:51.316 is seen in about 25 to 50% of the cases. 00:25:52.166 --> 00:25:57.233 So part of 11 the end of 11 goes to 18. 00:25:57.233 --> 00:26:00.916 And then a little bit of 18 goes back to 11. 00:26:02.033 --> 00:26:05.483 Our marginal zone B-cell lymphoma 00:26:06.866 --> 00:26:11.566 is an interface between the non lymphoid red pulp 00:26:11.566 --> 00:26:14.666 and the lymphoid white pulp are trisomy 00:26:14.666 --> 00:26:17.666 three and trisomy. 00:26:18.150 --> 00:26:20.550 Our trisomy three and our translocation 00:26:20.550 --> 00:26:24.800 1118 rarely occur in this marginal zone. 00:26:24.800 --> 00:26:26.000 B-cell lymphoma. 00:26:27.416 --> 00:26:29.516 Follicular lymphomas make up 00:26:29.516 --> 00:26:35.216 about 35% of our non-Hodgkin lymphoma cases in the US, 00:26:35.666 --> 00:26:40.850 and about 22% of the world wide non-Hodgkin lymphoma, 00:26:41.550 --> 00:26:44.550 so it's the second most common form. 00:26:46.283 --> 00:26:48.766 Translocation 1418 00:26:48.766 --> 00:26:52.650 is seen in about 70 to 95% of the cases. 00:26:53.116 --> 00:26:54.800 So here's my translocation. 00:26:54.800 --> 00:26:58.500 14 1818 ends up too short, 00:26:58.666 --> 00:27:03.200 14 ends up too long with this extra dark band here 00:27:04.616 --> 00:27:08.416 there is a variant of my translocation 00:27:08.416 --> 00:27:13.133 1418 and it's a between £0.02 00:27:13.616 --> 00:27:16.500 and 18 00:27:16.500 --> 00:27:19.500 for secondary sided genetic changes. 00:27:19.550 --> 00:27:24.350 We do see in about 90% of cases of follicular lymphoma, 00:27:24.866 --> 00:27:27.950 we're going to have gains of X chromosome, 00:27:28.350 --> 00:27:31.350 chromosome 712 and 18 00:27:32.000 --> 00:27:34.700 rearrangements involving BCL six. 00:27:34.700 --> 00:27:37.950 It's 3Q273Q28 00:27:38.716 --> 00:27:42.383 variable deletions of 6Q23 to q 00:27:42.383 --> 00:27:46.800 to six in about 10 to 40% of cases 00:27:47.816 --> 00:27:51.900 for follicular lymphomas in transformation, 00:27:51.900 --> 00:27:57.450 we're going to see deletions of £0.17 again with Tp53 00:27:57.866 --> 00:28:02.450 and also deletions of £0.09, which is CDK into a. 00:28:04.916 --> 00:28:06.833 Mantle cell lymphomas are 00:28:06.833 --> 00:28:11.266 about 3 to 10% of our non-Hodgkin lymphoma cases. 00:28:11.850 --> 00:28:15.866 The median survival is between 3 to 5 years. 00:28:16.700 --> 00:28:19.766 Translocation 1114 is seen in 00:28:19.766 --> 00:28:23.000 about 70 to 75% of the cases. 00:28:23.566 --> 00:28:26.450 So chromosome 11 breaks here 00:28:26.450 --> 00:28:29.250 goes to chromosome 1414. 00:28:29.250 --> 00:28:33.616 It's the very end that breaks and goes back to my 11. 00:28:33.616 --> 00:28:37.283 I can't really see that piece, but I can clearly see 00:28:37.283 --> 00:28:40.283 the piece of 11 on 14. 00:28:40.400 --> 00:28:43.916 It's results in a, fusion 00:28:43.916 --> 00:28:48.416 between BCL one or CCN, D1 and IG, 00:28:49.400 --> 00:28:51.716 and it is something that can be detected 00:28:51.716 --> 00:28:55.250 frequently by fish for secondary terms. 00:28:55.950 --> 00:28:59.366 Chromosome changes I have trisomy 12, 00:28:59.666 --> 00:29:04.650 the deleted £0.17, deleted £0.09, and deleted 13. 00:29:04.650 --> 00:29:06.383 That we've talked about. 00:29:06.383 --> 00:29:11.000 There is a blast droid variant that I frequently see with tetra platy 00:29:12.533 --> 00:29:13.883 trisomy 12. 00:29:13.883 --> 00:29:17.550 Complex carry types are loss of 17, P 00:29:17.850 --> 00:29:20.700 and Tp53 are associated 00:29:20.700 --> 00:29:23.700 with an adverse prognosis. 00:29:24.350 --> 00:29:29.266 Diffuse large B-cell lymphoma, or Dlbcl, 00:29:29.633 --> 00:29:34.016 make up about 35% of our non-Hodgkin lymphoma cases. 00:29:34.733 --> 00:29:37.016 20 to 30% of those 00:29:37.016 --> 00:29:42.166 will have this translocation between chromosome 14 and 18. 00:29:43.250 --> 00:29:46.016 30% will have BCL 00:29:46.016 --> 00:29:49.016 six rearrangements at three q to seven, 00:29:49.516 --> 00:29:53.566 and it's also associated frequently with complex carrier types. 00:29:54.150 --> 00:29:58.883 So again, for my 14, 18, 18 ends up two short, 00:29:59.333 --> 00:30:03.083 14 has this extra long band down here. 00:30:04.283 --> 00:30:08.100 This is an example of a BCL six rearrangement. 00:30:08.100 --> 00:30:12.533 In this particular one it paired with chromosome 22. 00:30:13.016 --> 00:30:16.016 So this is chromosome 22. 00:30:16.200 --> 00:30:19.316 Part of three breaks off and goes to my 22. 00:30:21.750 --> 00:30:24.000 There's also double hit lymphomas. 00:30:24.000 --> 00:30:27.166 And double hit lymphomas are an aggressive 00:30:27.166 --> 00:30:30.383 type of B-cell non-Hodgkin lymphomas. 00:30:31.133 --> 00:30:34.733 They're characterized by rearrangements involving MC 00:30:35.450 --> 00:30:38.033 at 8Q2 for an either 00:30:38.033 --> 00:30:41.783 BCL two egg chromosome 18 or less 00:30:41.783 --> 00:30:46.133 frequently, BCL six on chromosome three q 00:30:47.666 --> 00:30:50.516 if the rearrangements are seen in all three. 00:30:50.516 --> 00:30:53.550 So I see rearrangements with 00:30:53.550 --> 00:30:56.550 MC, BCL two and BCL six. 00:30:56.933 --> 00:31:01.400 It's called a triple hit lymphoma, which is less rare than the double hit. 00:31:02.250 --> 00:31:05.183 The signs and symptoms of double hit 00:31:05.183 --> 00:31:10.500 lymphomas may mimic Burkitt lymphoma or Dlbcl. 00:31:10.500 --> 00:31:13.766 Our large B-cell lymphoma. 00:31:14.633 --> 00:31:17.633 Here's the translocation three eight. 00:31:19.166 --> 00:31:21.600 So it's the bottom of three 00:31:21.600 --> 00:31:24.600 and the bottom of eight. 00:31:24.600 --> 00:31:29.150 So it's between BCL six and MC. 00:31:29.933 --> 00:31:34.950 The translocation 814 that we talked about before which involves 00:31:34.950 --> 00:31:38.900 MC and the translocation 1418, 00:31:38.900 --> 00:31:41.900 which involves BCL two. 00:31:42.766 --> 00:31:45.150 Some other large B-cell lymphoma 00:31:45.150 --> 00:31:48.683 are mediastinal thymic large B-cell lymphoma. 00:31:49.400 --> 00:31:54.266 Those are going to involve a hyper diploid with gains of £0.09 00:31:55.216 --> 00:31:58.433 intravascular large B-cell lymphomas 00:31:58.733 --> 00:32:01.733 with that are within small vessels. 00:32:02.266 --> 00:32:05.266 For these, there's very little organ involvement. 00:32:05.850 --> 00:32:09.316 But it can affect the central nervous system and the skin 00:32:10.433 --> 00:32:11.300 and primary 00:32:11.300 --> 00:32:14.633 fusion lymphomas, which are HIV associated. 00:32:16.200 --> 00:32:18.150 Kaspersky's sarcoma 00:32:18.150 --> 00:32:21.900 associated herpes virus or human herpesvirus 00:32:21.900 --> 00:32:26.900 eight, is something that is associated with the primary effusion, lymphomas. 00:32:27.466 --> 00:32:30.050 They can also be malignant effusions 00:32:30.050 --> 00:32:33.050 that don't have a tumor mass. 00:32:34.200 --> 00:32:37.500 This is just to review our lymphoma translocation. 00:32:37.500 --> 00:32:42.416 So again my mult or mucosal associated lymphoid tissue 00:32:42.950 --> 00:32:46.666 lymphoma is going to be translocation 1118. 00:32:47.150 --> 00:32:53.033 That's the gene CCN D1 BCL two are follicular lymphoma 00:32:53.033 --> 00:32:58.650 or translocation 1418 between IGA and BCL two. 00:32:59.333 --> 00:33:05.400 Our mantle cell lymphomas which are translocations between 11 and 14 00:33:05.850 --> 00:33:11.116 cc and D1 and IGA, are my genes for those Burkitt 00:33:11.116 --> 00:33:15.566 lymphoma is translocation 814, which is MC IGA. 00:33:16.666 --> 00:33:18.866 Our diffuse large B-cell 00:33:18.866 --> 00:33:23.400 lymphomas are going to be variable partners 00:33:23.400 --> 00:33:28.050 with the translocation of BCL six on chromosome three. 00:33:29.066 --> 00:33:31.050 Our double hit lymphomas 00:33:31.050 --> 00:33:36.083 are MC and BCL two or BCL six. 00:33:36.683 --> 00:33:39.683 And then our nodal marginal zone B-cell lymphoma 00:33:39.833 --> 00:33:42.833 don't have recurrent abnormalities. 00:33:43.616 --> 00:33:43.950 All right. 00:33:43.950 --> 00:33:47.400 Our mature T-cell in case the leukemias. 00:33:49.433 --> 00:33:53.333 They're derived from mature post thymic T-cells. 00:33:53.866 --> 00:33:57.150 The EnCase cells share very similar immuno 00:33:57.150 --> 00:34:00.800 phenotypic and functional properties with the T cells. 00:34:00.800 --> 00:34:03.500 So they're all kind of lumped together. 00:34:03.500 --> 00:34:06.266 They're relatively uncommon neoplasms. 00:34:06.266 --> 00:34:11.000 They only make up about 12% of all non-Hodgkin lymphoma cases. 00:34:11.750 --> 00:34:14.066 I've given you an example of a 00:34:14.066 --> 00:34:18.116 T cell lymphoma that has skin infiltration. 00:34:18.116 --> 00:34:21.116 So what you would see on the surface of the skin, 00:34:22.066 --> 00:34:24.833 there are risk factors for T cell. 00:34:24.833 --> 00:34:29.183 And in case cell leukemias or lymphomas, the human 00:34:29.183 --> 00:34:33.800 T cell leukemia virus positivity is one. 00:34:33.800 --> 00:34:38.516 So if their patients are positive for that virus it's a risk factor. 00:34:39.200 --> 00:34:43.350 It is more common in Asian and Native American populations. 00:34:43.350 --> 00:34:47.566 One of the things that we're going to see is excess basal fills. 00:34:50.550 --> 00:34:52.883 For our types of T cell. 00:34:52.883 --> 00:34:57.166 And in case of leukemias, we're going to have a leukemic 00:34:57.166 --> 00:35:02.066 disseminated the T cell pro lymphocytic leukemia 00:35:02.066 --> 00:35:06.500 which is an aggressive subset of chronic lymphocytic leukemia. 00:35:07.400 --> 00:35:11.716 Our T cell large granular lymphocytic leukemia, 00:35:12.166 --> 00:35:15.233 which has generally an indolent disease course, 00:35:15.866 --> 00:35:20.600 are aggressive in cell leukemias, which has a strong association 00:35:20.933 --> 00:35:23.783 with the Epstein-Barr virus. 00:35:23.783 --> 00:35:25.966 Our adult T cell leukemia 00:35:25.966 --> 00:35:31.216 lymphoma, which has a casual agent with the human T-cell 00:35:31.216 --> 00:35:34.216 leukemia virus type one. 00:35:35.400 --> 00:35:37.100 Some recurrent alterations 00:35:37.100 --> 00:35:40.366 that we see in our mature T and NK cells. 00:35:40.800 --> 00:35:45.266 Again, we're going to see things with our T cell receptor gene loci 00:35:45.616 --> 00:35:49.283 map 214 Q11 .27, 00:35:49.283 --> 00:35:52.800 P1415 and 7235. 00:35:53.516 --> 00:35:56.416 We're going to see variable abnormalities 00:35:56.416 --> 00:35:59.416 involving these T cell gene loci. 00:35:59.483 --> 00:36:01.850 We may see an inverted 14. 00:36:01.850 --> 00:36:08.666 That's pretty common in about 80% of abnormal t PLL cases. 00:36:09.266 --> 00:36:12.650 A translocation 1414 is seen 00:36:12.650 --> 00:36:16.500 in about 10% of t PLL cases. 00:36:17.266 --> 00:36:20.366 PLL is the pro lymphocytic leukemia. 00:36:21.233 --> 00:36:24.233 Trisomy three and trisomy seven are common. 00:36:24.800 --> 00:36:27.416 An ISO chromosome seven Q 00:36:27.416 --> 00:36:30.416 or an ISIL chromosome eight q. 00:36:30.500 --> 00:36:33.350 So again, those are going to be made up 00:36:33.350 --> 00:36:37.616 of two long arms of chromosome seven or chromosome eight. 00:36:38.866 --> 00:36:39.383 Thank you.