Acute promyelocytic leukemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

There are several broad classification schemes for acute promyelocytic leukemia. The most well-accepted classification scheme is risk-based classification, which categories patients into low-risk, intermediate-risk, or high-risk based on the white blood cell count and platelet count. Another classification scheme is based on the origin of the leukemia, which categorized patients as having de novo or therapy-related disease. A final classification scheme is cytogenetic-based, in which case specific chromosomal abnormalities are used to stratify patients.

Classification

Based on Risk

Based on etiology

  • De novo disease:
    • De novo acute promyelocytic leukemia is the most common subtype.
    • This refers to development of the disease in the absence of prior cytotoxic therapy or prior precursor conditions.
    • De novo acute promyelocytic leukemia is due to a sporadic events in cells, without prior DNA damaging insults. This is in contrast to therapy-related disease.
  • Therapy-related disease:
    • Therapy-related disease refers to the development of acute promyelocytic leukemia in patients who were previously treated with DNA-damaging or genotoxic agents for other conditions, such as other cancers.
    • The most common DNA-damaging agents that cause therapy-associated acute promyelocytic leukemia are topoisomerase inhibitors and alkylating agents.
    • Therapy-related acute promyelocytic leukemia is typically seen in patients with a history of breast cancer who received cyclophosphamide or patients with a history of a germ cell tumor who have received etoposide.
    • The prognosis of therapy-related disease is worse than that of de novo disease, with a 5-year survival of less than 10 years. The 4-year overall survival for therapy-related disease is 24.5%, compared to 39.5% for de novo disease.[3]
Chemotherapeutic agents
Topoisomerase II inhibitors:
Alkylating agents:
Other chemotherapeutic agents:

Based on cytogenetics

  • The karyotype of most cases of acute promyelocytic leukemia involves the t(15;17) translocation between the PML and RARA genes. However, complex karyotypes may co-exist in some cases of acute promyelocytic leukemia.[5]
Cytogenetics
Complex karyotype
Trisomy 8
Tetraploidy
  • Tetraploidy is defined as the presence of four sets of chromosomes in a cell.
  • Tetraploidy is generally rare in acute promyelocytic leukemia and accounts for approximately 0.75% of cases.
  • The karyotype of most cases of acute promyelocytic leukemia involves the t(15;17) translocation between the PML and RARA genes.
  • However, complex karyotypes may co-exist in some cases of acute promyelocytic leukemia.
  • Tetraploidy in acute promyelocytic leukemia is more commonly associated with CD2 expression in the malignant cells.
  • Tetraploid acute promyelocytic leukemia is mostly sensitive to all-trans retinoic acid.[5]
t(8;21)
  • The t(8;21) translocation sometimes co-exists with the t(15;17) translocation.
  • The t(8;21) translocation is more commonly found in acute myeloid leukemia and involves the juxtaposition of the ETO (RUNX1T1) gene on chromosome 8 with AML1 (RUNX1) gene on chromosome 21.
  • A total of six cases of coexisting t(8;21) and t(15;17) have thus far been described.[6]

References

  1. 1.0 1.1 Coombs CC, Tavakkoli M, Tallman MS (2015). "Acute promyelocytic leukemia: where did we start, where are we now, and the future". Blood Cancer J. 5: e304. doi:10.1038/bcj.2015.25. PMC 4450325. PMID 25885425.
  2. McCulloch D, Brown C, Iland H (2017). "Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives". Onco Targets Ther. 10: 1585–1601. doi:10.2147/OTT.S100513. PMC 5359123. PMID 28352191.
  3. 3.0 3.1 Zhang YC, Zhou YQ, Yan B, Shi J, Xiu LJ, Sun YW; et al. (2015). "Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report". World J Gastroenterol. 21 (14): 4402–7. doi:10.3748/wjg.v21.i14.4402. PMC 4394105. PMID 25892894.
  4. 4.0 4.1 Zahid MF, Parnes A, Savani BN, Litzow MR, Hashmi SK (2016). "Therapy-related myeloid neoplasms - what have we learned so far?". World J Stem Cells. 8 (8): 231–42. doi:10.4252/wjsc.v8.i8.231. PMC 4999650. PMID 27621757.
  5. 5.0 5.1 5.2 5.3 5.4 Chen C, Huang X, Wang K, Chen K, Gao D, Qian S (2018). "Early mortality in acute promyelocytic leukemia: Potential predictors". Oncol Lett. 15 (4): 4061–4069. doi:10.3892/ol.2018.7854. PMC 5835847. PMID 29541170.
  6. Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M (July 1993). "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript". EMBO J. 12 (7): 2715–21. PMC 413521. PMID 8334990.

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