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Molecular biology of acute promyelocytic leukemia

Wendy Stock, MD
Michael J Thirman, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Acute myeloid leukemia (AML) refers to a group of hematopoietic neoplasms involving cells committed to the myeloid lineage. Acute promyelocytic leukemia (APL) is a biologically and clinically distinct variant of AML. In the World Health Organization classification system, APL is classified as acute promyelocytic leukemia with PML-RARA; it was previously classified as AML-M3 in the older French-American-British (FAB) classification system [1,2]. (See "Classification of acute myeloid leukemia".)

The cytogenetic hallmark of APL is a translocation involving RARA, the retinoic acid receptor alpha locus on chromosome 17 [3]. The vast majority of cases of APL contain t(15;17)(q24.1;q21.1). However, several variant translocations involving RARA have been identified, including t(11;17) and t(5;17) [4-6], and distinguishing between these translocations is important because patients with the variant translocation t(11;17) are almost invariably resistant to all-trans retinoic acid (ATRA) [4,5,7]. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults" and "Initial treatment of acute promyelocytic leukemia in adults".)

The molecular biology of APL will be discussed here. The molecular biology of acute myeloid leukemias other than APL and of ALL is discussed separately. (See "Pathogenesis of acute myeloid leukemia" and "Cytogenetics and molecular genetics in acute lymphoblastic leukemia" and "Molecular genetics of acute myeloid leukemia".)


Retinoic acid (RA) is a critical ligand in the differentiation of multiple tissues, mediated through binding to a retinoic acid receptor (RAR). RARs belong to the nuclear steroid/thyroid hormone receptor superfamily. Of the three RAR isoforms, RAR alpha is expressed primarily in hematopoietic cells.

RAR alpha is a member of a family of retinoid-binding transcription factors (including RXR) that regulate gene expression. RAR alpha contains discrete functional domains, including an amino terminal transcriptional activation domain, and DNA-binding, dimerization, and retinoid-binding domains. RAR alpha heterodimerizes with retinoid X receptor (RXR), and binds to RA-responsive elements to regulate transcription of target genes [7].


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Literature review current through: Jul 2017. | This topic last updated: Aug 10, 2017.
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