Molecular biology of acute promyelocytic leukemia
- Wendy Stock, MD
Wendy Stock, MD
- Professor of Medicine
- Pritzker School of Medicine of the University of Chicago
- Michael J Thirman, MD
Michael J Thirman, MD
- Associate Professor of Medicine
- Pritzker School of Medicine of the University of Chicago
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 . 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 AND THE RETINOIC ACID RECEPTOR
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 .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- RETINOIC ACID AND THE RETINOIC ACID RECEPTOR
- t(15;17) THE USUAL TRANSLOCATION IN APL
- The PML gene
- The fusion genes of t(15;17)
- - Mechanism of action of PML/RARA
- VARIANT TRANSLOCATIONS
- PLZF/RARA and t(11;17)
- NPM/RARA and t(5;17)
- NuMA/RARA and t(11;17)
- STAT5B/RARA and interstitial chromosome 17 deletion
- BCOR/RARA and t(X;17)(q11;q21.1)
- FLT3 MUTATION
- RESISTANCE TO RETINOIC ACID TREATMENT