Elsevier

Seminars in Hematology

Volume 50, Issue 4, October 2013, Pages 271-283
Seminars in Hematology

Special Article: 50 Years of Seminars in Hematology
Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

https://doi.org/10.1053/j.seminhematol.2013.09.006Get rights and content

Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic example of targeted therapy in cancer to date is the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI), which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered.

Section snippets

CML Frontline Treatment Options

Three TKIs are commercially available for the frontline treatment of CML: imatinib, dasatinib, and nilotinib. Current guidelines endorse all three as excellent options for the initial management of CML in the chronic phase (CML-CP) (Table 1). Imatinib mesylate (Gleevec, Novartis Pharmaceutical Corp, East Hanover, NJ), was the first TKI to receive approval by the US Food and Drug Administration (FDA) for the treatment of patients with CML-CP. It acts via competitive inhibition at the adenosine

Should We Strive for an Earlier and Deeper Response?

Beyond cytogenetic response, the more stringent criteria of a molecular response (MR) may also offer prognostic information. Recently, much attention has focused on the potential for an early MR as indicative of favorable long-term outcomes, including survival, and for guiding treatment decisions.

The potential significance of MMR has been investigated extensively. Some studies noted that achievement of MMR at 12 or 18 months was not associated with any benefit in long-term OS, although other

FLT3 Inhibitors

FLT3, a receptor tyrosine kinase involved in cell signaling and proliferation, is expressed on the surface of AML cells.62 Because FLT3 is often mutated in AML blasts, investigators explored FLT3’s influence on AML pathophysiology and prognosis, and developed targeting new molecules to target FLt3 mutations. Two distinct types of activating mutations are internal tandem duplication (ITD) of the intracellular juxtamembrane region and point mutations in the tyrosine kinase domain (TKD). FLT3 ITDs

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    Conflicts of interest: Consultancy: Novartis, Pfizer, Baris, Ariad, Teva.

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