Acute promyelocytic leukemia pathophysiology

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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

Overview

The pathophysiology of acute promyelocytic leukemia is most commonly due to a reciprocal translocation between chromosomes 15 and 17. The novel gene product causes a differentiation block in myeloid cells. There are multiple different binding partners for the RARA gene, so multiple translocations can contribute to the pathogenesis of acute promyelocytic leukemia.

Pathophysiology

Translocation Partner Chromosomal Location Function Response to Therapy Other Features

PML

15q24.1

  • A member of the tripartite motif (TRIM) family
  • Localizes to nucleolar bodies and functions as a transcription factor and tumor suppressor
  • Regulate p53 response to oncogenic growth signals
  • Influenced by the cell cycle

PLZF (ZBTB16)[2][8]

11q23.2

NPM1

5q35.1

  • Encodes nucleophosmin 1 (a nucleolar shuttle protein)
  • Involved in centromere duplication
  • Serves a protein chaperone
  • Regulates the cell cycle
  • Sequesters the tumor suppressor ARF in the nucleus and protects ARF from degradation

NUMA[7]

11q13.4

STAT5B[8]

17q21.2

References

  1. Zelent, Arthur; Guidez, Fabien; Melnick, Ari; Waxman, Samuel; Licht, Jonathan D (2001). "Translocations of the RARα gene in acute promyelocytic leukemia". Oncogene. 20 (49): 7186–7203. doi:10.1038/sj.onc.1204766. ISSN 0950-9232.
  2. 2.0 2.1 2.2 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.
  3. L. R. Hiorns, T. Min, G. J. Swansbury, A. Zelent, M. J. Dyer & D. Catovsky (1994). "Interstitial insertion of retinoic acid receptor-alpha gene in acute promyelocytic leukemia with normal chromosomes 15 and 17". Blood. 83 (10): 2946–2951. PMID 8180390. Unknown parameter |month= ignored (help)
  4. Falchi L, Verstovsek S, Ravandi-Kashani F, Kantarjian HM (2016). "The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy". Cancer. 122 (8): 1160–8. doi:10.1002/cncr.29852. PMC 5042140. PMID 26716387.
  5. "RARA retinoic acid receptor alpha [Homo sapiens (human)] - Gene - NCBI".
  6. Saeed, S; Logie, C; Stunnenberg, H G; Martens, J H A (2011). "Genome-wide functions of PML–RARα in acute promyelocytic leukaemia". British Journal of Cancer. 104 (4): 554–558. doi:10.1038/sj.bjc.6606095. ISSN 0007-0920.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Park J, Jurcic JG, Rosenblat T, Tallman MS (2011). "Emerging new approaches for the treatment of acute promyelocytic leukemia". Ther Adv Hematol. 2 (5): 335–52. doi:10.1177/2040620711410773. PMC 3573416. PMID 23556100.
  8. 8.0 8.1 8.2 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.

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