Abstract
Purpose of review Since the 1970s, the concept of differentiation therapy has been viewed as a promising and revolutionary approach for the treatment of acute myeloid leukemia (AML) and other cancers. However, the successful clinical application of differentiation therapy has only been realized since the late 1980s and only in one subtype of AML, acute promyelocytic leukemia (APL). The use of all-trans-retinoic acid (ATRA) and arsenic trioxide, both of which induce degradation of the progressive multifocal leukoencephalopathy/retinoic acid receptor α oncoprotein, in combination with chemotherapy is currently the accepted treatment of APL, presenting a potential paradigm for differentiation therapy in clinical oncology. Recent findings We have begun to understand why ATRA fails to induce differentiation in AML The underlying reasons identified thus far are associated with an inability to target the removal of leukemogenic fusion proteins, aberrant epigenetic regulation of genes involved in the ATRA signaling pathway and the presence of factors that interfere with proper retinoic acid receptor α function. Summary Here, we examine the reasons why the exquisite sensitivity of APL to ATRA-based differentiation therapy has not been extended to other of AML subtypes. Current differentiation-based combinatorial approaches to target AML will also be analyzed. Finally, we will evaluate the potential of novel strategies, high-throughput screening, and functional genomics to uncover new differentiation-based therapies for AML.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 84-91 |
| Number of pages | 8 |
| Journal | Current Opinion in Hematology |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2009 |
| Externally published | Yes |
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Keywords
- Acute myeloid leukemia
- All-trans-retinoic acid
- Differentiation therapy
- Retinoic acid receptor α
ASJC Scopus subject areas
- Hematology
Cite this
Differentiation therapy of acute myeloid leukemia : Past, present and future. / Petrie, Kevin; Zelent, Arthur Z; Waxman, Samuel.
In: Current Opinion in Hematology, Vol. 16, No. 2, 03.2009, p. 84-91.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differentiation therapy of acute myeloid leukemia
T2 - Past, present and future
AU - Petrie, Kevin
AU - Zelent, Arthur Z
AU - Waxman, Samuel
PY - 2009/3
Y1 - 2009/3
N2 - Purpose of review Since the 1970s, the concept of differentiation therapy has been viewed as a promising and revolutionary approach for the treatment of acute myeloid leukemia (AML) and other cancers. However, the successful clinical application of differentiation therapy has only been realized since the late 1980s and only in one subtype of AML, acute promyelocytic leukemia (APL). The use of all-trans-retinoic acid (ATRA) and arsenic trioxide, both of which induce degradation of the progressive multifocal leukoencephalopathy/retinoic acid receptor α oncoprotein, in combination with chemotherapy is currently the accepted treatment of APL, presenting a potential paradigm for differentiation therapy in clinical oncology. Recent findings We have begun to understand why ATRA fails to induce differentiation in AML The underlying reasons identified thus far are associated with an inability to target the removal of leukemogenic fusion proteins, aberrant epigenetic regulation of genes involved in the ATRA signaling pathway and the presence of factors that interfere with proper retinoic acid receptor α function. Summary Here, we examine the reasons why the exquisite sensitivity of APL to ATRA-based differentiation therapy has not been extended to other of AML subtypes. Current differentiation-based combinatorial approaches to target AML will also be analyzed. Finally, we will evaluate the potential of novel strategies, high-throughput screening, and functional genomics to uncover new differentiation-based therapies for AML.
AB - Purpose of review Since the 1970s, the concept of differentiation therapy has been viewed as a promising and revolutionary approach for the treatment of acute myeloid leukemia (AML) and other cancers. However, the successful clinical application of differentiation therapy has only been realized since the late 1980s and only in one subtype of AML, acute promyelocytic leukemia (APL). The use of all-trans-retinoic acid (ATRA) and arsenic trioxide, both of which induce degradation of the progressive multifocal leukoencephalopathy/retinoic acid receptor α oncoprotein, in combination with chemotherapy is currently the accepted treatment of APL, presenting a potential paradigm for differentiation therapy in clinical oncology. Recent findings We have begun to understand why ATRA fails to induce differentiation in AML The underlying reasons identified thus far are associated with an inability to target the removal of leukemogenic fusion proteins, aberrant epigenetic regulation of genes involved in the ATRA signaling pathway and the presence of factors that interfere with proper retinoic acid receptor α function. Summary Here, we examine the reasons why the exquisite sensitivity of APL to ATRA-based differentiation therapy has not been extended to other of AML subtypes. Current differentiation-based combinatorial approaches to target AML will also be analyzed. Finally, we will evaluate the potential of novel strategies, high-throughput screening, and functional genomics to uncover new differentiation-based therapies for AML.
KW - Acute myeloid leukemia
KW - All-trans-retinoic acid
KW - Differentiation therapy
KW - Retinoic acid receptor α
UR - http://www.scopus.com/inward/record.url?scp=62249169964&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62249169964&partnerID=8YFLogxK
U2 - 10.1097/MOH.0b013e3283257aee
DO - 10.1097/MOH.0b013e3283257aee
M3 - Article
C2 - 19468269
AN - SCOPUS:62249169964
VL - 16
SP - 84
EP - 91
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
SN - 1065-6251
IS - 2
ER -