TY - JOUR
T1 - Novel postremission strategies in adults with acute myeloid leukemia
AU - Lancet, Jeffrey E.
AU - Karp, Judith E.
PY - 2009/3
Y1 - 2009/3
N2 - Purpose of review Given the high rates of relapse in acute myeloid leukemia (AML), there is tremendous opportunity for the development of new therapeutic strategies in the postremission state. Unfortunately, the currently available modalities for postremission therapy, namely chemotherapy, have proven largely ineffective in changing the natural history of AML. The challenges to overcome therapeutic failure in the minimal residual disease status may relate to an incomplete understanding of the mechanisms and cell populations that are directly related to disease relapse as well as suboptimal ability to identify patients at highest risk for relapse. Recent findings Being a heterogeneous disease, relapsed AML is unlikely to emanate from one predominant mechanism; instead, there are likely multiple biologic factors at play that allow for clinical relapse to occur. These factors likely include multidrug resistance proteins, aberrant signal transduction pathways, survival of leukemia stem cells, microenvironmental interactions, and immune tolerance. Many novel strategies are in development that target these mechanisms, ranging from chemotherapeutic modalities, to signal transduction inhibitors, to upregulation of antileukemic immune responses. Summary Understanding the underlying mechanisms of leukemic cell survival and resistance has spurred the development of novel therapeutic approaches to overcome these mechanisms in the hope of eradicating minimal residual disease and improving survival in AML
AB - Purpose of review Given the high rates of relapse in acute myeloid leukemia (AML), there is tremendous opportunity for the development of new therapeutic strategies in the postremission state. Unfortunately, the currently available modalities for postremission therapy, namely chemotherapy, have proven largely ineffective in changing the natural history of AML. The challenges to overcome therapeutic failure in the minimal residual disease status may relate to an incomplete understanding of the mechanisms and cell populations that are directly related to disease relapse as well as suboptimal ability to identify patients at highest risk for relapse. Recent findings Being a heterogeneous disease, relapsed AML is unlikely to emanate from one predominant mechanism; instead, there are likely multiple biologic factors at play that allow for clinical relapse to occur. These factors likely include multidrug resistance proteins, aberrant signal transduction pathways, survival of leukemia stem cells, microenvironmental interactions, and immune tolerance. Many novel strategies are in development that target these mechanisms, ranging from chemotherapeutic modalities, to signal transduction inhibitors, to upregulation of antileukemic immune responses. Summary Understanding the underlying mechanisms of leukemic cell survival and resistance has spurred the development of novel therapeutic approaches to overcome these mechanisms in the hope of eradicating minimal residual disease and improving survival in AML
KW - Acute myeloid leukemia
KW - Leukemia stem cell
KW - Minimal residual disease
KW - Postremission therapy
KW - Targeted therapy
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U2 - 10.1097/MOH.0b013e3283257b04
DO - 10.1097/MOH.0b013e3283257b04
M3 - Review article
C2 - 19468272
AN - SCOPUS:62249220561
SN - 1065-6251
VL - 16
SP - 105
EP - 111
JO - Current opinion in hematology
JF - Current opinion in hematology
IS - 2
ER -