WEBVTT 00:00:08.566 --> 00:00:11.700 Hi. Today we're going to start talking about leukemias. 00:00:11.733 --> 00:00:15.766 So we're going to talk about CML, MDS and AML. 00:00:19.266 --> 00:00:19.566 All right. 00:00:19.566 --> 00:00:22.800 Chronic my logged in as leukemia or CML 00:00:24.733 --> 00:00:27.900 leukemia is found in the blood and bone marrow. 00:00:28.033 --> 00:00:32.233 It's a rapid production of a high number of abnormal white cells. 00:00:32.666 --> 00:00:36.866 Those white cells don't have the ability to fight infection well. 00:00:37.433 --> 00:00:39.900 And it also impairs the ability 00:00:39.900 --> 00:00:42.900 of the bone marrow to produce 00:00:43.200 --> 00:00:46.200 red blood cells and platelets. 00:00:47.100 --> 00:00:50.100 Lymphoma is abnormal lymphocytes 00:00:50.166 --> 00:00:53.366 that collect in the lymphatic system. 00:00:53.900 --> 00:00:56.833 It also impairs your immune system. 00:00:56.833 --> 00:01:01.000 Myeloma is the abnormal proliferation of plasma cells. 00:01:01.466 --> 00:01:04.266 Plasma cells are white blood cells that produce 00:01:04.266 --> 00:01:07.266 disease and infection fighting antibodies. 00:01:07.600 --> 00:01:10.500 It prevents the normal production of antibodies 00:01:10.500 --> 00:01:13.800 and also leaves the immune system weak and susceptible. 00:01:18.366 --> 00:01:20.600 For chronic myelogenous leukemia. 00:01:20.600 --> 00:01:22.900 A lot of patients don't have symptoms. 00:01:22.900 --> 00:01:28.000 When it's diagnosed, it's picked up something abnormal is picked up 00:01:28.000 --> 00:01:31.500 during an, blood test during a routine physical. 00:01:32.000 --> 00:01:34.800 They may see mild anemia or persistent 00:01:34.800 --> 00:01:37.800 anemia, which is a decrease in RBCs. 00:01:38.100 --> 00:01:43.200 They may see, leukocyte ptosis, which is an increase in the white cell 00:01:43.200 --> 00:01:46.400 count, and also thrombocytopenia, 00:01:46.400 --> 00:01:49.400 which is a decrease in platelets. 00:01:49.466 --> 00:01:53.300 100% of CML patients will have the translocation. 00:01:53.300 --> 00:01:58.000 922 right now in the world, there's between 1.2 00:01:58.000 --> 00:02:02.166 to 1.5 million people that are currently living with CML. 00:02:03.000 --> 00:02:06.900 If we look at the chromosomes, you may notice at the bottom of chromosome 00:02:06.900 --> 00:02:09.900 nine seems a little bit more fluffy. 00:02:09.900 --> 00:02:11.400 Then there's homolog. 00:02:11.400 --> 00:02:15.766 And then if you look at chromosome 22, he's pretty obvious. 00:02:15.766 --> 00:02:18.200 You'll notice that he is much shorter. 00:02:19.366 --> 00:02:19.766 That's 00:02:19.766 --> 00:02:23.133 because a little bit of nine went to 22, 00:02:23.133 --> 00:02:26.133 and a lot of 22 went to chromosome nine. 00:02:28.033 --> 00:02:29.600 The genetic changes for 00:02:29.600 --> 00:02:33.000 CML was first identified in 1960, 00:02:33.366 --> 00:02:37.666 and they identified the derivative chromosome 22. 00:02:38.066 --> 00:02:41.900 If you look at this picture, that's what they were looking at in 1960. 00:02:41.900 --> 00:02:43.700 This was pre banding. 00:02:43.700 --> 00:02:46.700 So they just had solid stained chromosomes. 00:02:47.433 --> 00:02:51.000 They called it the Philadelphia chromosome because it was discovered 00:02:51.000 --> 00:02:54.000 and identified at the University of Pennsylvania. 00:02:54.500 --> 00:02:56.900 It wasn't until 1973 00:02:56.900 --> 00:03:00.366 that it was identified to be part of a translocation. 00:03:01.200 --> 00:03:03.500 That's because banding first started 00:03:03.500 --> 00:03:06.700 about 1971 1972. 00:03:07.600 --> 00:03:12.133 In 1984, the genes BCR and Abell were identified, 00:03:12.300 --> 00:03:15.133 and in 2001, CML 00:03:15.133 --> 00:03:18.133 became the first human all logical disorder 00:03:18.333 --> 00:03:22.200 to have a drug developed specifically to treat it. 00:03:22.800 --> 00:03:27.333 Gleevec was developed to block the effect of the fusion gene product 00:03:27.966 --> 00:03:30.966 on these translocations, when they developed 00:03:31.000 --> 00:03:34.000 a fusion between two genes. 00:03:34.033 --> 00:03:37.633 You're not only getting a lack of the protein 00:03:37.633 --> 00:03:41.366 that gene should have produced, but you're also 00:03:41.733 --> 00:03:45.400 producing an abnormal protein that shouldn't have been there. 00:03:47.566 --> 00:03:50.666 CML is considered a biphasic disease. 00:03:50.900 --> 00:03:55.366 The chronic phase is generally between 3 to 5 years in duration. 00:03:55.866 --> 00:03:59.666 The only abnormality that we're going to see is the translocation. 00:04:00.266 --> 00:04:03.800 Then there can be an accelerated or transformation 00:04:03.800 --> 00:04:06.800 phase, which is 6 to 9 months in duration. 00:04:07.400 --> 00:04:10.400 The number of abnormal cells will increase 00:04:11.366 --> 00:04:14.100 over 20% hour. 00:04:14.100 --> 00:04:19.133 One or more additional chromosome abnormalities start to appear. 00:04:20.000 --> 00:04:23.200 The blasting phase is about 3 to 6 months. 00:04:23.200 --> 00:04:24.400 Survival. 00:04:24.400 --> 00:04:27.200 You have complete transformation to acute 00:04:27.200 --> 00:04:30.200 leukemia with more than 20% blast. 00:04:30.833 --> 00:04:35.166 And usually we see multiple secondary abnormalities present. 00:04:35.833 --> 00:04:38.633 Some of the common secondary abnormalities 00:04:38.633 --> 00:04:42.900 include plus eight a gain of the extra derivative 00:04:42.900 --> 00:04:46.533 Philadelphia chromosome for the derivative. 00:04:46.533 --> 00:04:52.233 Chromosome 22 plus 19 an ISO 17 q 00:04:52.900 --> 00:04:56.566 which results in a deletion or loss of 17 PE. 00:04:56.600 --> 00:04:59.600 So we have a loss of p53 00:05:00.000 --> 00:05:03.000 and then translocation 321, 00:05:03.300 --> 00:05:08.300 which results in a fusion between a TBI one and AML one. 00:05:11.166 --> 00:05:14.266 Now on the first slide for CML, 00:05:14.266 --> 00:05:17.433 I say to 100% of CML patients 00:05:17.433 --> 00:05:22.666 are going to have the translocation 922 but by chromosomes 00:05:22.666 --> 00:05:26.100 we do see a Philadelphia negative CML. 00:05:26.600 --> 00:05:28.566 How does that happen? 00:05:28.566 --> 00:05:31.500 We can have a subtle or invisible 00:05:31.500 --> 00:05:34.500 cryptic insertion by site of genetics. 00:05:34.900 --> 00:05:39.000 So by chromosomes nine and 22 look normal. 00:05:39.600 --> 00:05:45.366 But if you do the fish you'll see the translocation between 9 and 22. 00:05:45.466 --> 00:05:49.100 It's not really an insertion as far as the mechanism goes. 00:05:49.200 --> 00:05:54.033 Generally what happens is that nine translates to 22. 00:05:54.833 --> 00:05:58.600 And then as part of our DNA 00:05:58.600 --> 00:06:03.600 repair and in checkpoints, it tries to translocate back, 00:06:03.966 --> 00:06:09.466 but it breaks below this fusion between 9 and 22 a bit low. 00:06:09.466 --> 00:06:12.500 The fusion of BCR and able. 00:06:13.900 --> 00:06:16.900 So again ABL goes to BCR 00:06:18.166 --> 00:06:20.100 and then it breaks down here 00:06:20.100 --> 00:06:24.233 below this translocation below the fusion. 00:06:24.600 --> 00:06:26.933 And it goes back. 00:06:26.933 --> 00:06:30.766 But I still have a BCR able fusion 00:06:32.300 --> 00:06:32.966 complex. 00:06:32.966 --> 00:06:36.533 Translocations happen also three way and four way 00:06:36.833 --> 00:06:41.566 that are visible by karyotype analysis but can sometimes be difficult 00:06:41.566 --> 00:06:44.566 to interpret without the Fish data. 00:06:46.133 --> 00:06:48.833 Here is a variant three way translocation. 00:06:48.833 --> 00:06:52.033 So nine went to 22. 00:06:52.066 --> 00:06:56.533 We see 22 is very short, just like my derivative 22 should be. 00:06:57.300 --> 00:06:59.933 22 went to chromosome 11. 00:06:59.933 --> 00:07:02.933 So here's the rest of chromosome 22. 00:07:03.166 --> 00:07:06.166 And then 11 went back to chromosome nine. 00:07:06.466 --> 00:07:10.866 If you remember when we talked about chromosome nomenclature 00:07:11.233 --> 00:07:15.433 we talked about complex rearrangements. 00:07:15.433 --> 00:07:17.666 Complex translocations. 00:07:17.666 --> 00:07:20.600 We start off with the lowest number follow 00:07:20.600 --> 00:07:23.633 where it went, follow where it went. 00:07:23.633 --> 00:07:26.633 And eventually something is going to go back to our first one. 00:07:26.933 --> 00:07:31.333 So this is written nine 2211. 00:07:33.400 --> 00:07:33.766 All right. 00:07:33.766 --> 00:07:36.766 My dysplastic syndrome or MDS. 00:07:37.833 --> 00:07:41.966 It's a group of disorders where the bone marrow does not function normally 00:07:42.600 --> 00:07:45.900 and it fails to produce enough healthy blood cells. 00:07:46.466 --> 00:07:50.000 It's characterized by chronic progressive side apnea. 00:07:50.033 --> 00:07:53.766 So anemia neutropenia and thrombocytopenia. 00:07:54.300 --> 00:07:58.733 But you also have bone marrow dysplasia or abnormal cell development. 00:07:59.700 --> 00:08:03.033 The bone marrow smears are usually normal to hyper 00:08:03.033 --> 00:08:06.600 cellular with less than 20% blasts. 00:08:07.300 --> 00:08:10.266 It involves defects in proliferation, 00:08:10.266 --> 00:08:13.333 differentiation, apoptosis, 00:08:13.666 --> 00:08:18.500 and it's going to evolve to AML or acute myelogenous leukemia. 00:08:18.900 --> 00:08:22.566 About 25 to 40% of the patients. 00:08:23.866 --> 00:08:27.200 It's generally a disease seen in older adults. 00:08:27.233 --> 00:08:30.233 The median age is about 70 years. 00:08:30.466 --> 00:08:33.966 It's also more frequently seen in men than women. 00:08:34.666 --> 00:08:39.433 The incidence in the general population is three per 100,000 people. 00:08:39.433 --> 00:08:42.466 But when I look at people over the age of 70, 00:08:43.000 --> 00:08:47.233 the incident rises 20 in 100,000 people. 00:08:48.100 --> 00:08:52.700 Secondary MDS and AML cases due to chemotherapy 00:08:52.700 --> 00:08:57.600 or radiation therapy for previous cancers do happen. 00:08:57.766 --> 00:09:00.600 It's about 10 to 15% 00:09:00.600 --> 00:09:04.333 of all MDS AML cases that this happens with 00:09:05.533 --> 00:09:06.633 major causes of 00:09:06.633 --> 00:09:10.300 death for MDS patients are infections 00:09:10.766 --> 00:09:13.833 and bleeding related to the bone marrow failure. 00:09:16.533 --> 00:09:16.933 All right. 00:09:16.933 --> 00:09:20.366 So for MDS and 00:09:21.600 --> 00:09:26.600 other leukemic classifications there are two different 00:09:26.600 --> 00:09:31.266 classification systems for B which is the French American British. 00:09:31.266 --> 00:09:33.733 It came out in 1982. 00:09:33.733 --> 00:09:37.733 And it's something that a lot of clinicians are moving away from. 00:09:38.066 --> 00:09:42.066 But it's a good idea to be familiar with it still, because we still have 00:09:42.066 --> 00:09:46.500 older physicians that use it, at least in the cited genetic lab. 00:09:46.500 --> 00:09:48.800 We still see it some. 00:09:48.800 --> 00:09:51.600 Who is the World Health Organization? 00:09:51.600 --> 00:09:58.233 And it described these hematological systems first in 1997. 00:09:58.233 --> 00:10:01.233 It was last updated in 2010. 00:10:01.533 --> 00:10:06.133 So for myelodysplastic syndrome, some of the ones that we're going to see 00:10:06.466 --> 00:10:11.633 are refractory anemia, refractory anemia with ring side arrow blast, 00:10:12.200 --> 00:10:15.566 refractory anemia with excess blasts. 00:10:16.666 --> 00:10:18.566 We can also see refractory 00:10:18.566 --> 00:10:23.533 anemia in transformation, and one that we don't really see 00:10:23.533 --> 00:10:28.566 written out much anymore is CML, which was in Fab classification. 00:10:29.033 --> 00:10:32.600 It was for chronic myeloma acidic leukemia. 00:10:33.066 --> 00:10:36.500 Now that's generally referred to as MDS. 00:10:36.500 --> 00:10:39.000 And MPD 00:10:39.000 --> 00:10:40.433 with Who. 00:10:40.433 --> 00:10:43.433 A lot of the classifications are the same. 00:10:43.566 --> 00:10:47.833 We do picked up refractory side apnea with multi lineage 00:10:47.833 --> 00:10:52.233 dysplasia and MDS with a deleted 00:10:52.233 --> 00:10:55.266 five is a new classification 00:10:57.066 --> 00:10:59.600 AML with multi lineage dysplasia. 00:10:59.600 --> 00:11:04.800 Following MDS is what used to be refractory 00:11:04.800 --> 00:11:08.033 anemia with excess blasts in transformation. 00:11:09.833 --> 00:11:13.000 All right, decided genetics of MDS is an integral 00:11:13.000 --> 00:11:17.833 part of the care in myelodysplastic syndrome one. 00:11:17.833 --> 00:11:21.333 It will help confirm the diagnosis that something is going on. 00:11:22.000 --> 00:11:25.966 They use the evaluation to assess the prognosis 00:11:27.000 --> 00:11:30.733 depending on the abnormality that's found. 00:11:31.066 --> 00:11:34.800 It gives them an idea of the risk of progression to AML. 00:11:35.300 --> 00:11:38.100 It's 25 to 40% of the patients 00:11:38.100 --> 00:11:41.100 that are going to progressed to AML, not all of them. 00:11:41.633 --> 00:11:45.000 It also can give them an overall expected survival. 00:11:46.266 --> 00:11:50.766 Recurring chromosome abnormalities at the time of diagnosis are between 00:11:50.766 --> 00:11:56.000 40 to 70% of primary MDS patients, or patients 00:11:56.000 --> 00:11:59.000 who haven't been diagnosed with anything before. 00:11:59.933 --> 00:12:02.100 95% of the patients 00:12:02.100 --> 00:12:05.700 that have treatment related MDS are going to have recurring 00:12:05.700 --> 00:12:09.433 chromosome abnormalities at the time of diagnosis. 00:12:10.233 --> 00:12:13.300 So why is the difference between treatment 00:12:13.300 --> 00:12:16.300 related and primary MDS patients? 00:12:16.666 --> 00:12:19.833 We do see a lot of patients for anemia 00:12:20.200 --> 00:12:22.966 or thrombocytopenia, that type of thing 00:12:22.966 --> 00:12:26.866 that don't really meet the criteria for MDS. 00:12:27.433 --> 00:12:29.900 They do a bone marrow really expecting 00:12:29.900 --> 00:12:33.200 normal results, hoping for normal results. 00:12:33.600 --> 00:12:37.166 They just kind of want to verify that nothing more is going on. 00:12:37.200 --> 00:12:41.833 That's something that we see, especially with persistent anemia. 00:12:44.033 --> 00:12:45.700 Five Q minus syndrome. 00:12:45.700 --> 00:12:50.400 So MDS with five q minus is generally seen 00:12:50.900 --> 00:12:53.866 middle aged elderly females. 00:12:53.866 --> 00:12:57.300 The progression is preceded by an increase in blast, 00:12:57.900 --> 00:13:02.666 which is also going to be accompanied by additional chromosome abnormalities. 00:13:03.433 --> 00:13:07.700 Now five Q minus can be a complete loss of the chromosome. 00:13:08.133 --> 00:13:09.900 The break points do vary. 00:13:09.900 --> 00:13:12.000 I've given you some examples here. 00:13:12.000 --> 00:13:15.966 At the bottom on this first example, I'm missing 00:13:15.966 --> 00:13:19.500 a large portion of the terminal end 00:13:20.533 --> 00:13:21.400 here. 00:13:21.400 --> 00:13:24.400 I'm missing from here on 00:13:24.633 --> 00:13:28.566 right here I'm missing. 00:13:28.566 --> 00:13:32.566 It's a little bit further down, but I'm missing the bottom here. 00:13:33.666 --> 00:13:36.766 And then here is one with the minimal region. 00:13:37.700 --> 00:13:41.533 Although the weight, although the break points vary, 00:13:41.533 --> 00:13:46.466 we do see a commonly deleted region of 5Q31 through 00:13:46.466 --> 00:13:52.000 335Q minus is associated with a long survival. 00:13:54.900 --> 00:13:56.700 Some common alterations that 00:13:56.700 --> 00:14:00.400 we see in MDS trisomy eight 00:14:00.966 --> 00:14:03.533 I deleted or minus 00:14:03.533 --> 00:14:08.433 some 7QA loss of chromosome five, 00:14:08.433 --> 00:14:11.433 or the deleted five q that we talked about. 00:14:12.066 --> 00:14:15.066 A deletion in 20 q 00:14:15.600 --> 00:14:18.733 minus y and ISO 17, 00:14:18.733 --> 00:14:22.300 which results in a loss of that p53 00:14:22.300 --> 00:14:25.300 gene on £0.17, 00:14:25.400 --> 00:14:28.800 the interstitial deletion on chromosome 13. 00:14:28.833 --> 00:14:34.066 So it's up toward the centromere region that's gone or also minus 00:14:34.066 --> 00:14:38.400 so many 13 deletion in chromosome 11 Q 00:14:38.933 --> 00:14:42.966 a deletion or translocation in £0.12. 00:14:45.266 --> 00:14:48.900 A deletion of nine Q which is a terminal deletion. 00:14:49.333 --> 00:14:52.100 An ISO dice centric X. 00:14:52.100 --> 00:14:58.033 For some balanced rearrangements, we see a translocation 13A 00:14:58.233 --> 00:15:01.400 translocation between chromosomes 211 00:15:02.200 --> 00:15:05.666 and inverted three, so the long arm of chromosome 00:15:05.666 --> 00:15:09.066 three has an inversion, causing an abnormal pattern 00:15:09.800 --> 00:15:12.133 and a translocation six nine. 00:15:13.933 --> 00:15:16.200 I've given you these again 00:15:16.200 --> 00:15:19.200 where they're a little bit larger and you can see them better. 00:15:20.266 --> 00:15:22.466 So the translocations 00:15:22.466 --> 00:15:25.466 are off over here to the right. 00:15:26.300 --> 00:15:30.533 You can see the deleted seven has a couple different break points 00:15:30.533 --> 00:15:33.533 that are also just like the deleted five 00:15:33.833 --> 00:15:36.666 trisomy eight, the deleted nine. 00:15:36.666 --> 00:15:37.800 Deleted 11. 00:15:37.800 --> 00:15:43.733 Deleted £0.12 r deletion of chromosome 13, our ISO £0.17 00:15:43.800 --> 00:15:46.800 and then deleted 20. 00:15:47.700 --> 00:15:48.466 For treatment 00:15:48.466 --> 00:15:52.266 related MDS, we see some of the same alterations 00:15:52.266 --> 00:15:56.966 like the minus seven deleted seven minus only five deleted five. 00:15:57.400 --> 00:16:00.300 We see a couple of different ones too, though 00:16:00.300 --> 00:16:03.300 we see this dice centric 517 00:16:04.400 --> 00:16:08.366 so this is chromosome 17 s long arm. 00:16:08.866 --> 00:16:13.000 And then chromosome five short arm together. 00:16:13.400 --> 00:16:18.000 You normally see that with one normal five and one normal 17. 00:16:18.333 --> 00:16:22.800 So we've got a loss of five Q and a loss of £0.17 00:16:23.300 --> 00:16:28.933 a whole arm translocation between chromosome one q and £0.07 00:16:30.300 --> 00:16:31.133 results in a 00:16:31.133 --> 00:16:34.666 loss of seven q and a gain of one q. 00:16:35.100 --> 00:16:37.833 So this is £0.07 with one q. 00:16:37.833 --> 00:16:40.833 I normally see it with two normal ones 00:16:40.866 --> 00:16:43.833 and one normal chromosome 17. 00:16:43.833 --> 00:16:47.366 Our 321, we saw in MDS 00:16:47.933 --> 00:16:51.033 we see a translocation here between chromosome 00:16:51.033 --> 00:16:54.566 11 q and £0.16. 00:16:55.266 --> 00:16:59.100 And another translocation that we see sometimes in treatment 00:16:59.100 --> 00:17:03.600 related MDS is a translocation between chromosome 00:17:03.600 --> 00:17:07.300 five q and 12 q. 00:17:11.000 --> 00:17:14.000 Again, here they are a little bit bigger. 00:17:15.566 --> 00:17:18.733 All right MDS progression to AML does 00:17:18.733 --> 00:17:23.466 happen in 25 to 45% of the patients. 00:17:24.266 --> 00:17:27.700 The threshold of 20% blast in the blood or bone 00:17:27.700 --> 00:17:30.700 marrow is the distinguishing characteristic 00:17:30.933 --> 00:17:33.833 between AML and MDS. 00:17:33.833 --> 00:17:37.466 So less than 20% blast is going to be MDS. 00:17:37.766 --> 00:17:39.533 More than 20% blast. 00:17:39.533 --> 00:17:41.333 It's going to be AML. 00:17:41.333 --> 00:17:45.200 AML can present with more than 20% blasts 00:17:45.200 --> 00:17:50.366 without having a previously recognized myelodysplastic phase. 00:17:50.733 --> 00:17:54.766 So not all AML patients go through the MDS. 00:17:55.933 --> 00:17:58.000 Here is a normal bone marrow smear. 00:17:58.000 --> 00:18:01.266 You can see these purple cells or white cells. 00:18:01.766 --> 00:18:04.766 We see a lot of red cells 00:18:05.166 --> 00:18:06.100 here. 00:18:06.100 --> 00:18:09.100 On the right is an abnormal blood smear. 00:18:09.100 --> 00:18:13.866 You can see one of the most notable things immediately is that I have a lot 00:18:13.866 --> 00:18:20.200 more of these purple white cells, but I also have a lot less of the red blood 00:18:20.200 --> 00:18:23.433 cells, even in the areas where the purple cells aren't. 00:18:25.400 --> 00:18:28.800 AML is acute myelogenous leukemia. 00:18:30.800 --> 00:18:35.633 The cited genetic results are part of staging and classification 00:18:35.633 --> 00:18:37.833 of the leukemia, 00:18:37.833 --> 00:18:41.666 the most common acute leukemia affecting adults, 00:18:41.933 --> 00:18:45.766 which is 80% in the United States, is AML. 00:18:46.300 --> 00:18:51.733 The incidence does increase with age for overall incidence and age. 00:18:52.133 --> 00:18:56.100 It's 1.8 cases per 100,000 people per year. 00:18:56.466 --> 00:18:59.466 For people less than the age of 65, 00:18:59.900 --> 00:19:03.133 that rises to 17.5 cases per 00:19:03.133 --> 00:19:06.600 100,000 over the age of 65. 00:19:07.033 --> 00:19:10.566 The median age at diagnosis is 68. 00:19:10.566 --> 00:19:15.233 And again, there are more males and females like we saw with MDS 00:19:17.166 --> 00:19:20.166 whose subtypes for AML. 00:19:20.400 --> 00:19:24.633 The first one is AML with characteristic genetic abnormalities. 00:19:25.300 --> 00:19:29.266 Those have a fairly high rate of remission, which is pretty good 00:19:29.733 --> 00:19:32.733 AML with the translocation. 821 00:19:33.733 --> 00:19:38.800 when we have AML with abnormal eosinophils, we tend to see 00:19:38.800 --> 00:19:41.800 rearrangements in chromosome 16, 00:19:41.933 --> 00:19:47.400 we can see an inverted 16 where I have a break in the p arm 00:19:47.400 --> 00:19:50.400 and the q arm and the middle inverts 00:19:50.466 --> 00:19:54.000 a translocation between my 216 homolog. 00:19:54.000 --> 00:19:57.000 So translocation 1616 00:19:57.900 --> 00:19:59.833 or across a deletion 00:19:59.833 --> 00:20:02.833 in the long arm of chromosome 16 00:20:04.033 --> 00:20:05.900 APL or acute pro 00:20:05.900 --> 00:20:09.000 Milosevic leukemia is characterized 00:20:09.000 --> 00:20:12.600 by a translocation between 15 and 17. 00:20:13.500 --> 00:20:17.033 Another translocation that we see in this 00:20:17.033 --> 00:20:20.100 Who subtype is a translocation 00:20:20.100 --> 00:20:23.100 between chromosomes nine and 11. 00:20:23.966 --> 00:20:26.033 This one, you really got to have 00:20:26.033 --> 00:20:28.866 good chromosome quality preparations for 00:20:30.633 --> 00:20:31.866 the end of chromosome 00:20:31.866 --> 00:20:35.333 nine peel and the bottom of chromosome 11. 00:20:35.733 --> 00:20:39.033 So the bottom of chromosome 11 ends a little dark. 00:20:39.966 --> 00:20:42.966 And the top of the nine ends light. 00:20:43.566 --> 00:20:46.400 Again it's pretty difficult to see on 00:20:46.400 --> 00:20:49.466 poor quality preparations, which we sometimes get. 00:20:51.900 --> 00:20:53.433 Another classification 00:20:53.433 --> 00:20:56.433 is AML with multi lineage dysplasia. 00:20:57.300 --> 00:21:01.000 That means it includes a prior myelodysplastic 00:21:01.000 --> 00:21:05.000 syndrome, MDS or Mylo proliferative disease. 00:21:05.000 --> 00:21:08.966 MPD that has transformed into AML. 00:21:09.433 --> 00:21:12.433 So it's not treatment related AML, 00:21:13.033 --> 00:21:16.400 it's just that it's had the prior MDS or MPD. 00:21:17.033 --> 00:21:20.033 Again, these are seen in elderly patients, 00:21:20.366 --> 00:21:23.366 generally with a poor prognosis. 00:21:24.300 --> 00:21:26.500 Then AML and MDS 00:21:26.500 --> 00:21:29.500 that's treatment or therapy related. 00:21:29.533 --> 00:21:34.100 So the patients have had prior chemotherapy and or radiation 00:21:34.533 --> 00:21:37.300 for a different primary cancer. 00:21:37.300 --> 00:21:40.600 They subsequently develop AML or MDS. 00:21:43.000 --> 00:21:44.833 These are going to be characterized 00:21:44.833 --> 00:21:47.833 by specific chromosome abnormalities 00:21:47.900 --> 00:21:50.900 and generally carry a worse prognosis. 00:21:51.166 --> 00:21:53.833 Our last two subtype is AML, 00:21:53.833 --> 00:21:56.833 not otherwise categorized. 00:21:57.600 --> 00:21:59.700 So AML with multi lineage 00:21:59.700 --> 00:22:05.066 dysplasia is going to have cited genetic abnormalities very similar to MDS. 00:22:05.066 --> 00:22:05.900 Right. 00:22:05.900 --> 00:22:09.700 It originated with MDS R minus seven. 00:22:09.700 --> 00:22:13.366 Deleted seven Q minus five deleted five q. 00:22:13.800 --> 00:22:18.333 I may see trisomy of chromosome eight, nine, 11, 00:22:18.733 --> 00:22:21.733 19 and 21. 00:22:21.966 --> 00:22:25.333 Either a deleted or translocated 11 q 00:22:25.866 --> 00:22:29.233 deleted or translocated £0.12 minor. 00:22:29.333 --> 00:22:33.233 So me 18 and my deleted 20 Q 00:22:34.500 --> 00:22:38.566 for rearrangements I see less frequently. 00:22:39.633 --> 00:22:43.866 I'm going to include the deer translocation to 11 00:22:44.400 --> 00:22:47.866 and the dir one seven that we talked about before. 00:22:48.733 --> 00:22:52.000 Three q abnormalities of 3Q2 1 to 00:22:52.000 --> 00:22:56.433 3 q 26.2 are also seen. 00:22:57.466 --> 00:22:58.633 Those can be seen 00:22:58.633 --> 00:23:01.633 as an inversion between the two. 00:23:01.700 --> 00:23:04.700 So here is my inverted chromosome three 00:23:05.266 --> 00:23:09.533 A translocation three three where part of one three goes to the other. 00:23:09.533 --> 00:23:13.833 Very little of the first three goes back, or an insertion 00:23:13.833 --> 00:23:18.133 three three for therapy related to translocation. 00:23:18.133 --> 00:23:23.333 321 here my chromosome three ends up short and fluffy, 00:23:23.333 --> 00:23:26.333 and 21 ends up much larger, 00:23:26.566 --> 00:23:29.566 and translocation three five. 00:23:29.900 --> 00:23:32.066 This is another one that is 00:23:32.066 --> 00:23:35.900 or can be kind of subtle in poor quality preparations. 00:23:36.300 --> 00:23:39.166 But this is the end of chromosome three. 00:23:39.166 --> 00:23:42.166 Not much of five went back to chromosome three. 00:23:44.633 --> 00:23:45.600 This is an example 00:23:45.600 --> 00:23:49.333 karyotype of AML with multi lineage dysplasia. 00:23:50.100 --> 00:23:53.100 I do have additional material 00:23:53.100 --> 00:23:57.133 on the bottom of my chromosome two which is not a recurrent rearrangement. 00:23:57.833 --> 00:24:00.133 I have minus three. 00:24:00.133 --> 00:24:06.066 I deleted five deleted 7QI minus so many nine 00:24:07.566 --> 00:24:09.233 I have a deleted 00:24:09.233 --> 00:24:13.366 £0.12 here -16. 00:24:14.033 --> 00:24:18.000 There's additional material on my chromosome 18 00:24:18.766 --> 00:24:22.066 and 19 -20. 00:24:22.766 --> 00:24:26.233 I have additional material on my chromosome 21 00:24:26.633 --> 00:24:30.066 and a marker that I don't know who it is 00:24:31.600 --> 00:24:34.600 for therapy related AML. 00:24:35.100 --> 00:24:36.933 It's going to develop after 00:24:36.933 --> 00:24:39.933 alkylating agent induced damage. 00:24:40.266 --> 00:24:43.100 Generally that's about 5 to 7 years 00:24:43.100 --> 00:24:46.100 after therapy for the primary malignancy. 00:24:46.833 --> 00:24:51.633 I can also have treatment related AML after DNA. 00:24:51.933 --> 00:24:56.333 Topol I summarize two agents that one has a shorter 00:24:56.333 --> 00:24:59.333 latency period of 12 to 18 months. 00:25:00.566 --> 00:25:01.066 Thank you.