Author/Authors :
Mali، نويسنده , , Raghuveer Singh and Ramdas، نويسنده , , Baskar and Ma، نويسنده , , Peilin and Shi، نويسنده , , Jianjian and Munugalavadla، نويسنده , , Veerendra and Sims، نويسنده , , Emily and Wei، نويسنده , , Lei and Vemula، نويسنده , , Sasidhar and Nabinger، نويسنده , , Sarah C. and Goodwin، نويسنده , , Charles B. and Chan، نويسنده , , Rebecca J. and Traina، نويسنده , , Fabiola and Visconte، نويسنده , , Valeria and Tiu، نويسنده , , Ramon V. and Lewis، نويسنده , , Timothy A. and Stern، نويسنده , , Andrew M. and Wen، نويسنده , , Qiang and Crispino، نويسنده , , John D. and Boswell، نويسنده , , H. Scott and Kapur، نويسنده , , Reuben، نويسنده ,
Abstract :
Summary
w constitutive activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase. Genetic or pharmacologic inhibition of ROCK in oncogene-bearing cells impaired their growth as well as the growth of acute myeloid leukemia patient-derived blasts and prolonged the life span of mice bearing myeloproliferative disease. Downstream from ROCK, rapid dephosphorylation or loss of expression of myosin light chain resulted in enhanced apoptosis, reduced growth, and loss of actin polymerization in oncogene-bearing cells leading to significantly prolonged life span of leukemic mice. In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans.
