Acute promyelocytic leukemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]
Pathophysiology
The pathophysiology of acute promyelocytic leukemia begins with a balanced reciprocal chromosomal translocation in hematopoietic stem cells. The chromosomal translocation involves the juxtaposition of the retinoic acid receptor-alpha gene (RARA) on the long arm of chromosome 17 with another gene, most commonly the promyelocytic leukemia gene (PML) on the long arm of chromosome 15.[1] The translocation is designated as t(15;17)(q22;q12). The PML-RARA fusion product is a transcriptional regulator and prevents myeloid differentiation. This is known as a differentiation block, since the cells are unable to differentiate into normal mature cells. The result of the chromosomal translocation is ineffective blood cell production and uncontrolled proliferation of malignant promyelocytes.[1] In 95% of cases of acute promyelocytic leukemia, the translocation involved PML and RARA. However, it is important to note that RARA has multiple other binding partners which can lead to the development or acute promyelocytic leukemia.
Four other gene rearrangements have been described in APL fusing RARα to promyelocytic leukemia zinc finger (PLZF or ZBTB16), nucleophosmin (NPM), nuclear matrix associated (NUMA), or signal transducer and activator of transcription 5b (STAT5B) genes., ZBTB16
| RARA Binding Partner | Chromosomal Location | Function | Other Features |
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PLZF (ZBTB16) |
11q23.2 |
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NPM1 |
5q35.1 |
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Mixed warm-antibody and cold-antibody type |
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References
- ↑ 1.0 1.1 Langabeer SE, Preston L, Kelly J, Goodyer M, Elhassadi E, Hayat A (2017). "Molecular Profiling: A Case of ZBTB16-RARA Acute Promyelocytic Leukemia". Case Rep Hematol. 2017: 7657393. doi:10.1155/2017/7657393. PMC 5424191. PMID 28529810.
- ↑ Randen U, Trøen G, Tierens A, Steen C, Warsame A, Beiske K; et al. (2014). "Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma". Haematologica. 99 (3): 497–504. doi:10.3324/haematol.2013.091702. PMC 3943313. PMID 24143001.
- ↑ Moncrieff RE (1975). "Paroxysmal cold hemoglobinuria-1975". West J Med. 123 (6): 477. PMC 1130418. PMID 18747599.
- ↑ Packman CH (2015). "The Clinical Pictures of Autoimmune Hemolytic Anemia". Transfus Med Hemother. 42 (5): 317–24. doi:10.1159/000440656. PMC 4678314. PMID 26696800.