Abstract
Differentiation and Cell Survival of Myeloid Leukemia Cells
Highlights
The lessons from these two therapeutic successes are not transferred to other subtypes of myeloid leukemia, as the molecular lesions that can be attacked to eradicate the malignant cells appear to be “moving targets.” The mutations vary from acute myeloid leukemia (AML) case to case; secondary mutations appear and are often multiple, so current therapy largely depends on “brute-force” cell killing by administration of highly toxic agents, which have varying differential sensitivity for leukemic and normal cells
Apart from the AML subtype characterized by the 15:17 chromosome translocation known as acute promyelocytic leukemia (APL), which has shown lasting remissions when treated with all-trans retinoic acid (ATRA), especially when supplemented with the mildly toxic compound arsenic trioxide (ATO), mortality from the disease remains high
Hughes summarize the current state of knowledge in a comprehensive review entitled “Retinoid differentiation therapy for common types of acute myeloid leukemia” and suggest ways in which retinoid-based therapies can be improved by the inclusion of additional agents to increase the sensitivity of APL cells towards ATRA
Summary
The lessons from these two therapeutic successes are not transferred to other subtypes of myeloid leukemia, as the molecular lesions that can be attacked to eradicate the malignant cells appear to be “moving targets.” The mutations vary from AML case to case; secondary mutations appear and are often multiple, so current therapy largely depends on “brute-force” cell killing by administration of highly toxic agents, which have varying differential sensitivity for leukemic and normal cells. The landscape of treatment for acute myeloid leukemia (AML) is currently a grim one.
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