Acute promyelocytic leukemia (APL) is associated with reciprocal and balanced chromosomal translocations always involving the retinoic acid receptor alpha (RARa) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes.
RARalpha fuses to the PML gene in the majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RARalpha and RARalpha-X fusion genes are generated encoding aberrant chimeric proteins that exert critical oncogenic functions.
Associations
mitoxantrone therapy for multiple sclerosis (18406875)
Cytogenetics
Acute promyelocytic leukemia (APL) is typically associated with the t(15;17) that generates the PML-RARA fusion protein.
Animal models have shown that although the fusion protein is necessary, it is insufficient for the development of APL, implying that additional mechanisms are responsible for full-blown leukemia.
CGH (16419057)
losses
- 1p36 loss
- 2p11 loss
- 16p loss
- 17p loss
gains
- 8p gain
- 8q gain
- 13q gain
These results suggest that chromosomal imbalances are largely absent in APL, although some nonrandom chromosomal imbalances could be linked to the development of APL in a limited number of cases.
References
Karnan S, Tsuzuki S, Kiyoi H, Tagawa H, Ueda R, Seto M, Naoe T. Genomewide array-based comparative genomic hybridization analysis of acute promyelocytic leukemia. Genes Chromosomes Cancer. 2006 Apr;45(4):420-5. PMID: 16419057
Sanz MA. Treatment of acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program 2006:147-55.
Reviews
Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008;111:2505-2515.
Lallemand-Breitenbach V, Zhu J, Kogan S, Chen Z, de The H. Opinion: how patients have benefited from mouse models of acute promyelocytic leukaemia. Nat Rev Cancer. 2005 Oct;5(10):821-7. PMID: 16175176
Zhu J, Chen Z, Lallemand-Breitenbach V, de The H. How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer. 2002 Sep;2(9):705-13. PMID: 12209159
Pandolfi PP. Oncogenes and tumor suppressors in the molecular pathogenesis of acute promyelocytic leukemia. Hum Mol Genet. 2001 Apr;10(7):769-75. PMID: 11257111
Lin RJ, Egan DA, Evans RM. Molecular genetics of acute promyelocytic leukemia. Trends Genet. 1999 May;15(5):179-84. PMID: 10322484
Scaglioni PP, Pandolfi PP. The theory of APL revisited. Curr Top Microbiol Immunol 2007;313:85-100. PMID: 17217040