In P210 (+) chronic myelogenous leukemia (CML), down-regulated PAK1 gene expressions may lead to the suppression of cell proliferation and promotion of apoptosis through phosphorylation of STAT5, with a reverse effect in P190 (+) acute lymphoblastic leukemia(ALL), especially acute B lymphoblastic leukemia (B-ALL).
Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.
STAT5 also plays a key role in the generation of B cell precursor acute lymphoblastic leukemia, whereby the BCR-ABL1 translocation or the collaboration of JAK2 mutations with overexpression of the thymic stromal lymphopoietin receptor CRLF2 results in constitutive STAT5 activation leading to cytokine-independent survival and growth of leukemic cells.
In addition, generation of Tg for both p210BCR/ABL and Notch1DeltaC developed ALL in a shortened period with Stat5 activation, demonstrating the cooperative oncogenicity of Notch1DeltaC/NICD Delta C with p210BCR/ABL involving Stat5-mediated pathway.