Molecular basis for the diagnosis and treatment of acute promyelocytic leukemia

Abstract

Acute promyelocytic leukemia is characterized by gene rearrangements that always involve the retinoic acid receptor alpha on chromosome 15. In the majority of patients t(15;17) is detected, which generates the promyelocytic leukemia gene/retinoic acid receptor alpha rearrangement. This rearrangement interacts with several proteins, including the native promyelocytic leukemia gene, thus causing its delocalization from the nuclear bodies, impairing its function. The immunofluorescence staining technique using the anti-PML antibody may be used to provide a rapid diagnosis and to immediately start therapy using all-trans retinoic acid. The experience of the International Consortium on Acute Promyelocytic Leukemia has demonstrated that early mortality was significantly reduced by adopting the immunofluorescence technique. All-trans retinoic acid combined with chemotherapy is the standard therapy; this promotes complete remission rates greater than 90% and cure rates of nearly 80%. However, early mortality is still an important limitation and hematologists must be aware of the importance of treating newly diagnosed acute promyelocytic leukemia as a medical emergency.

Crosstalk between hnRNP K and SET in ATRA‐induced differentiation in acute promyelocytic leukemia

“…We propose that cell differentiation occurred, at least partly, by the decrease in PML-RARa oncoprotein and HDAC1 corepressor. The decrease in PML-RARa levels is a critical event to restore the transcription of RARa target genes [44]. During granulocyte differentiation, C/EBPa levels decrease in the early stages and PU.1 levels increase in the late stages under ATRA treatment [45].…”

Oral manifestations of acute promyelocytic leukemia: A case report

“…APL is a subtype of acute myeloid leukemia (AML) characterized by infiltration of bone marrow by dysplastic promyelocytes, a unique t(15;17) chromosomal translocation that generates a fusion transcript joining the PML (promyelocyte) and RAR-α (retinoic acid receptor-α) genes, and frequent association with bleeding disorders secondary to DIC [13]. Early detection of APL is important because of the high risk of early death due to severe hemorrhagic events, but current therapy with ATRA, which is a form of vitamin A, combined with chemotherapy results in 70% to 90% survival and disease-free outcome after five years [11,13].…”

“…Leukemia is a hematological disorder that is caused by an abnormal increase of immature white blood cells and is often associated with oral manifestations such as mucosal pallor, ecchymoses, bleeding, ulceration, gingival enlargement, trismus, mental nerve neuropathy, facial palsy, and infections [1][2][3][4][5][6][7][8][9][10][11][12]. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), and early detectionof APL is important because of the high risk of early death due to severe hemorrhagic events [13].…”

The Guidelines Project: Brazilian guidelines for acute promyelocytic leukemia

“…Its molecular bases are well defined, with different variations influencing the treatment of patients. 9 The results, as reported by the International Consortium on APL, established the treatment strategies and the conduct for the disease in developing countries. 10 , 11 …”