Chronic myelogenous leukemia, variant

Kurzrock R, Kloetzer WS, Talpaz M, Blick M, Walters R, Arlinghaus RB, Gutterman JU. Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia. Blood 1987 70 233-6. 

RIO. Robinson, J. C., Pierce, J. E., and Goldstein, D. P., Leucocyte alkaline phosphatase Electrophoretic variants associated with chronic myelogenous leukemia. Science 160, 58-60 (1965). 

Uehara, Y., Casa, S., Makita, A., Sakurada, K., and Miyazaki, T., Lysosomal arylsulfatases of human leukocytes Increment of phosphorylated B variant in chronic myelogenous leukemia. Cancer Res. 43, 5618-5622 (1983). 

A small-molecule inhibitor of Abl (STI-571) is effective in the treatment of chronic myelogenous leukemia CML, which is caused by the inadvertent activation of Abl. The crystal structure of the catalytic domain of Abl, complexed to a variant of STI-571, was reported. Critical to the binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located activation loop is not phosphorylated. The confoimation of this loop is distinct from tliat in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that... 

B. After chronic exposure, hematologic disorders such as pancytopenia, aplastic anemia, acute myelogenous leukemia, and its variants may occur. Causality is suspected for chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin s disease, and paroxysmal nocturnal hemoglobinuria. There is unproven association between benzene exposure and acute lymphoblastic leukemia, myelofibrosis, and lymphomas. Chromosomal abnormalities have been reported, although no effects on fertility have been described in women after occupational exposure. 

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