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ALK Inhibitor May Treat Rare Leukemia Cells with ALK Mutations

Dr. Jeffrey Tyner, PhD, an Assistant Professor at Oregon Health Science University in Portland, and colleagues reported that leukemia may respond to the treatment of drugs specifically targeting mutations in the anaplastic lymphoma kinase gene (ALK). This study was recently published in Cancer Research last month.

Dr. Jeffrey Tyner and colleagues carried out their study on 185 patients. 38 of them were with myeloproliferative neoplasms, 51 were with acute lymphoid leukemia and 96 were with acute myelogenous leukemia (AML). Deep sequencing of 1862 kinase and kinase-related genes using bone marrow and blood samples from the patient were performed by Dr. Jeffrey Tyner and team. Their analysis showed that ALK point mutations were heterozygous for two patients. One was an adult with AML and the other was a pediatric patient with B-cell lymphoblastic leukemia. Dr. Jeffrey Tyner and colleagues introduced the ALK mutations into laboratory-grown leukemia cells that are dependent on growth factor cytokine IL3 for growth to determine whether the ALK mutations were oncogenic. Their findings revealed that cells with ALK mutations have the ability to grow even in the absence of growth factor cytokine IL3. These findings highly suggest that ALK mutations could encourage abnormal cell growth. Then, Dr. Jeffrey Tyner and team continued to study the effect of ALK inhibitors inhibiting cells that have ALK mutations. Their laboratory studies revealed that ALK mutations in both patients were sensitive to ALK kinase inhibitors such as the FDA-approved drugs ceritinib and crizotinib. Another four other ALK inhibitors that are still in the stage of development were also effective in inhibiting cells that have ALK mutations. Further details on the study result can be found here.

Dr. Wendy Stock, MD, Professor of Medicine and Director of the Leukemia Program at the University of Chicago, uninvolved in this study commented that the findings in this study are interesting. However, she added that this study showed very preliminary evidence regarding ALK inhibitors as a therapeutic strategy for rare cases of leukemia that harbor ALK mutations.

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