Cytokines May Play Role in Gleevec Resistant Leukemia
Hematopoietic microenvironment affects drug sensitivity
FRIDAY, Sept. 7 (HealthDay News) -- Chemicals produced by the immune system, known as cytokines, may play a role in cases of B cell acute lymphocytic leukemia (B-ALL) resistance to Gleevec, according to a report published online Sept. 7 in Genes and Development.
To investigate why some cases of B-ALL are resistant to the cancer drug Gleevec, Charles J. Sherr, M.D., Ph.D., and colleagues from St. Jude Children's Research Hospital in Memphis, Tenn., generated mouse bone marrow cells that lacked the Arf tumor suppressor gene and produced the BCR-ABL kinase.
The researchers found that these B cells could continuously self-renew and caused rapid, fatal lymphoblastic leukemia when transplanted into healthy mice. These leukemias were resistant to Gleevec (imatinib), which targets BCR-ABL. In contrast, pre-B cell leukemias from bone marrow progenitors from immunodeficient mice that produced BCR-ABL and lacked Arf and the gamma chain common to cytokine receptors were more sensitive to Gleevec.
The crucial cytokine may be interleukin-7, the authors suggest, which is important for B cell development.