Acute promyelocytic leukemia pathophysiology: Difference between revisions
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==Pathophysiology== | ==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.<ref name="pmid28529810">{{cite journal| author=Langabeer SE, Preston L, Kelly J, Goodyer M, Elhassadi E, Hayat A| title=Molecular Profiling: A Case of ZBTB16-RARA Acute Promyelocytic Leukemia. | journal=Case Rep Hematol | year= 2017 | volume= 2017 | issue= | pages= 7657393 | pmid=28529810 | doi=10.1155/2017/7657393 | pmc=5424191 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28529810 }} </ref> 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.<ref name="pmid28529810">{{cite journal| author=Langabeer SE, Preston L, Kelly J, Goodyer M, Elhassadi E, Hayat A| title=Molecular Profiling: A Case of ZBTB16-RARA Acute Promyelocytic Leukemia. | journal=Case Rep Hematol | year= 2017 | volume= 2017 | issue= | pages= 7657393 | pmid=28529810 | doi=10.1155/2017/7657393 | pmc=5424191 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28529810 }} </ref> 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''), nucleophosmin (''NPM''), nuclear matrix associated (''NUMA''), or signal transducer and activator of transcription 5b (''STAT5B'') genes. | 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 | ||
The resultant fusion proteins disrupt the function of RARα which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving ''RARα'' is believed to be the initiating event, additional mutations are required for the development of leukemia. | The resultant fusion proteins disrupt the function of RARα which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving ''RARα'' is believed to be the initiating event, additional mutations are required for the development of leukemia. | ||
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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
The resultant fusion proteins disrupt the function of RARα which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving RARα is believed to be the initiating event, additional mutations are required for the development of leukemia.
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.