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Acute Lymphoblastic Leukemia

 

 

 

Cytogenetics and Molecular Genetics

 

The diagnostic bone marrow aspirate is also sent for routine cytogenetic analysis and for specialized molecular genetics tests which may include FISH (Fluorescence In-Situ Hybridization) and RT-PCR (Reverse Transcriptase Polymerase Chain Reaction).

About 90% of childhood ALL will have genetic abnormalities, some of which are recurrent among cases.  These may include:

  • Too many (hyperdiploid) or too few (hypodiploid) numbers of chromosomes
  • Chromosomal translocations
  • Portions of chromosomes being deleted
  • Ring chromosomes 

Most of these can be detected by routine G-banding on a metaphase chromosome spread (routine karyotyping).

Some of these genetic changes involve known genes with prognostic significance and therefore molecular genetics tests are used to define and confirm the gene is interrupted or to find changes not picked up on routine karyotyping.

Genetic changes are being used to define prognostic groups at time of diagnosis and dictate certain chemotherapy protocols which may involve either less intensive, more intensive (including upfront bone marrow transplant), or alternative therapies.

 

Examples of genetic changes in ALL:

Genetic Change

Comments

Translocation between chromosomes 12 and 21
  • Most common cytogenetic feature in ALL 

 

  • Translocates TEL gene onto AML1 gene 

 

  • Generally considered a FAVORABLE prognostic feature with excellent long term survival 

 

  • Considered standard-risk LOW on contemporary clinical trials with >90% long term survival provided:
  • CNS negative
  • Rapid early response to chemotherapy
  • No minimal residual disease at end of induction

 

Trisomies of chromosomes 4, 10, 18 (so called “triple trisomies”)
  • Presence of all 3 trisomies is generally a FAVORABLE prognostic feature with excellent long term survival

 

  • Considered standard-risk LOW on contemporary clinical trials as above

 

11q23 abnormalities (e.g. translocation between 4th and 11th chromosome)
  • Disruption of MLL (mixed lineage leukemia) gene 

 

  • Generally an UNFAVORABLE feature but this is dependent upon the age of the child (very unfavourable for infants as opposed to older children) and the response to initial chemotherapy

 

Translocation between chromosomes 9 and 22
  • "Philadelphia Chromosome" commonly associated with adult chronic myelogenous leukemia 

 

  • Translocates BCR gene onto ABL gene 

 

  • Uniformly UNFAVORABLE prognostic feature and dictates matched sibling BMT in first remission 

 

  • Targeted therapies (e.g. imatinib) against BCR-ABL showing excellent initial response in PH+ ALL

 

Hypodiploidy (<44 chromosomes)
  • UNFAVORABLE feature with high relapse rates 

 

  • Dictates BMT in first remission

 
iAMP21

 

 

 

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