Ph+ ALL: drawing strength from a benign past by Markus Müschen Blood Volume 125(19):2879-2880 May 7, 2015 ©2015 by American Society of Hematology

Survival and proliferation of normal mouse pre-B cells are promoted by IL-7R signaling and activation of JAK and STAT5 (A). Survival and proliferation of normal mouse pre-B cells are promoted by IL-7R signaling and activation of JAK and STAT5 (A). After malignant transformation of pre-B cells by BCR-ABL1 (Ph+ ALL), IL-7R signaling becomes redundant in ALL cells (B). Mallampati et al show that TKIs of BCR-ABL1 (eg, dasatinib) may effectively block BCR-ABL1 tyrosine kinase activity but concurrently induce IL-7 secretion in MSCs. TKI-induced IL-7 secretion by MSCs can, hence, restore IL-7R–mediated survival and proliferation signaling in Ph+ ALL cells (C). Although reinstatement of IL-7R and JAK signaling as in normal pre-B cells induces drug resistance, dual targeting of both BCR-ABL1 (eg, dasatinib) and JAK (eg, ruxolitinib) activity can prevent IL-7R-JAK–dependent survival signaling and short-circuit drug resistance (D). Markus Müschen Blood 2015;125:2879-2880 ©2015 by American Society of Hematology