Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia

Figures & data

Table I.  Expression of SFKs in hematopoietic cells [39].

Lineage	SFK member
T cells	Fyn, Lck
B cells	Blk, Fgr, Fyn, Lyn
Myeloid cells	Fgr, Hck, Lyn

SFK, Src-family kinase.

Figure 1. SFKs directly interact with BCR-ABL resulting in (1) activation of SFKs [17],[18],[25] and (2) augmentation of BCR-ABL kinase activity [49]. Activated SFKs work cooperatively with BCR-ABL in facilitating the growth and progression of leukemia [48],[50],[51]. Several downstream effectors of SFKs have been proposed to mediate the proleukemic effects, such as (3) STAT5 [50], which is known to activate genes involved in growth factor independence, differentiation, adhesion, and DNA repair [36],[52-54] and (4) AKT [55], which is key in regulating cell proliferation and survival in BCR-ABL – dependent cells [56]. (5) Active SFKs also phosphorylate certain tyrosine residues on BCR-ABL to create a binding site for GRB-2. This adaptor protein may link the BCR-ABL pathway to Ras, which is known to activate the MEK/ERK oncogenic signaling cascade [17],[48].

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