Acute promyelocytic leukemia: where did we start, where are we now, and the future

Abstract

Historically, acute promyelocytic leukemia (APL) was considered to be one of the most fatal forms of acute leukemia with poor outcomes before the introduction of the vitamin A derivative all-trans retinoic acid (ATRA). With considerable advances in therapy, including the introduction of ATRA initially as a single agent and then in combination with anthracyclines, and more recently by development of arsenic trioxide (ATO)-containing regimens, APL is now characterized by complete remission rates of 90% and cure rates of ∼80%, even higher among low-risk patients. Furthermore, with ATRA–ATO combinations, chemotherapy may safely be omitted in low-risk patients. The disease is now considered to be the most curable subtype of acute myeloid leukemia (AML) in adults. Nevertheless, APL remains associated with a significant incidence of early death related to the characteristic bleeding diathesis. Early death, rather than resistant disease so common in all other subtypes of AML, has emerged as the major cause of treatment failure.

Unusual Morphology in A Case of AML With t(8;21):A Diagnostic Dilemma

“…Morphologically it is consistent with FAB M3 [7].The cells from almost all patients have a balanced reciprocal translocation between chromosomes 15 and17, which generates a fusion transcript joining the PML (promyelocyte) and RAR-α (retinoic acid receptor-α) genes [8]. Leukemicpromyelocytes have the unique ability to undergo differentiation with exposure to retinoic acid and both differentiation and apoptosiswith exposure to arsenic trioxide (ATO) [9]. Thus, over the past 50 years APL has transformed from a highly fatal disease to highly curable one [9].…”

“…Leukemicpromyelocytes have the unique ability to undergo differentiation with exposure to retinoic acid and both differentiation and apoptosiswith exposure to arsenic trioxide (ATO) [9]. Thus, over the past 50 years APL has transformed from a highly fatal disease to highly curable one [9].…”

Therapy-related myelodysplastic syndrome after successful treatment of acute promyelocytic leukemia: case report and literature review

“…The higher incidence of APL in younger patients (starting with the second decade of life) is well known, and decreases after the age of 60 [25,26,27]. For patients who develop t-MNs during the CR of APL, the median age at APL diagnosis was 50 years old (18-68 years) [7] and 52 years (18-86 years) [19].…”

Small Molecule Inhibitors for Acute Myeloid Leukemia: Where is the Field Heading?

“…Young (<1 year old) age [8] and older age are widely recognized risk factors for one of the major causes of therapeutic failure in AML; that patients are not able to tolerate the toxicity associated with the most intensive chemotherapeutic treatment regimes, resulting in an increased rate of early death. The second major cause of therapeutic failure is relapse due to therapeutic resistance [9], which is particularly significant in acute promyelocytic leukemia [10,11], a subtype of AML.The incidence and mortality rate, potential for resistance, and limited therapeutic options combine to make the discovery of alternative chemotherapeutics critical for patients, particular infants and those older than 65, diagnosed with AML. To date, the use of alternative chemotherapeutics in AML has been largely disappointing [4].…”

“…Young (<1 year old) age [8] and older age are widely recognized risk factors for one of the major causes of therapeutic failure in AML; that patients are not able to tolerate the toxicity associated with the most intensive chemotherapeutic treatment regimes, resulting in an increased rate of early death. The second major cause of therapeutic failure is relapse due to therapeutic resistance [9], which is particularly significant in acute promyelocytic leukemia [10,11], a subtype of AML.…”