The cytogenetics of childhood acute leukemia

Published on May 31, 2016   52 min

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0:00
My name is Susana Raimondi. I work at St. Jude Children's Research Hospital. I'm the director of the Cytogenetics Laboratory, and the presentation today will be about the cytogenetics of childhood acute leukemias.
0:17
Regarding the topic today, the molecular changes occur at the chromosome level, at the gene level, or DNA sequences. A full range of genetic abnormalities is indicative of cancer, but many of the chromosomal alterations observed by conventional cytogenetics alone do not induce leukemia. Sometimes, there are no obvious chromosomal alterations. And some microscopic genetics alterations may be of leukemogenic/actionable events.
0:54
Regarding the cytogenetics of acute lymphoblastic leukemia,
1:00
when we consider the pediatric population, about 15% of the cases are T-lineage. They do have recurring chromosomal aberrations. However, they do not have impact on the clinical behavior of these patients with T-lymphoblastic leukemia. There's others that have B-lineage leukemia. About 50% of the cases have either hyperdiploid with greater than 50 chromosomes, or a translocation that is cryptic that is called t 12;21. The other subsets are smaller. And some of them are strongly associated with very poor prognosis.
1:50
The genetic classifications. We work with favorable prognoses and adverse prognoses. Favorable prognoses are the translocation 12;21 and the hyperdiploid with 51 to 67 chromosomes. Adverse prognosis is subclassification, subgroup of early T-cell precursor ETP, which is diagnosed by flow cytometry. And I will not further explain that subgroup. Other subgroup, a small one, is the amplification of ABL1 with a NUP214 on the 9q. And that is observed in T-cells ALLs associated with a poor outcome. The translocation 9;22 BCR-ABL has improved prognosis with ABL inhibitors. 11 q23 aberrations of MLL gene have very poor prognosis, especially in infants less than six months and with a high white blood cell count. Hyperdiploidy with less than 44 chromosomes, the amplification of a gene on 21q RUNX1, and the translocation 1;19 also associated with a higher risk of CNS relapse. And in the recent years, there are a lot of new molecular markers.
3:27
When we talk about the cytogenetics or genomics of pediatrics ALL, what I would like to bring in the presentation is the important cytogenetics or FISH subgroups that may need to be done complementary to detect the 12:21, the amplification of 21q, and hyperdiploidy. These are aberrations. 12;21 very frequent, greater than 20% of the cases. But it's cryptic. Therefore, we need to use other techniques, like FISH or a PCR in order to detect it. The amplification of the 21 also is abnormality that we need to work with FISH. And for hyperdiploidy, we need to be careful counting the chromosomes. Then, there are other novel subgroups that they have been discovered by genomic methods. And these are at high risk acute lymphoblastic leukemias and they're called Philadelphia-like. And by examples, they have mutations of JAK1 or JAK2 in down syndromes and non-down syndromes ALL, Ikaros deletions also in the high-risk ALLs. And all of them affect the CRLF2-JAK-STAT signaling in B-cell precursors ALL. Recently, discover numerous kinase-associated translocations. Most of these translocations are detected via next-generation sequencing.
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The cytogenetics of childhood acute leukemia

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