Rac in p190-BCR-ABL0Induced Leukemia.
Update 6/2014:
The following publications were supported completely or partly by funding from ALSF:
Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival.
Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu MN, Ficker AM, Dunn SK, Kuenzi AM, Arnett JL, Santho RA, Agirre X, Perentesis JP, Deininger MW, Zheng Y, Bustelo XR, Williams DA, Cancelas JA.
Blood. 2012 Jul 26;120(4):800-11.
On how Rac controls hematopoietic stem cell activity.
Cancelas JA.
Transfusion. 2011 Nov;51 Suppl 4:153S-159S
Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo.
Sengupta A, Arnett J, Dunn S, Williams DA, Cancelas JA.
Blood. 2010 Jul 8;116(1):81-4.
Rho GTPases in hematopoietic stem cell functions.
Cancelas JA, Williams DA.
Curr Opin Hematol. 2009 Jul;16(4):249-54.
Project Goal
We hypothesize that:
- Rac GTPases constitute a novel class of therapeutic targets in BCR- ABL-mediated leukemias;
- Specific BCR-ABL-dependent Rac activators cause the selective induction of lymphoid progenitor proliferation in p190 BCR-ABL+ ALL; and
- Since patient prognosis with p190 BCR/ABL+ ALL is extremely poor and these patients respond poorly to specific BCR-ABL tyrosine kinase inhibitors like imatinib, we believe that Rac may constitute a novel, significant molecular target in the therapy of p190-BCR/ABL+-ALL patients.
