A. CRLF2 overexpression in B-ALL may lead to aberrant signaling through mechanisms involving mutationally activated (red) JAK2, CRLF2, or other unknown kinases. Thus, CRLF2-overexpressng B-ALL patients may benefit from therapeutic use of anti-CRLF2 antibodies or small molecule kinase inhibitors. This model, based on that put forth by Hertzberg et al., includes estimated percentage ranges based on published data for both B-ALL and DS-ALL (6). B. Overexpression of CRLF2 may lead to aberrant signaling through monomeric, homodimeric, or heterodimeric receptor configurations of wildtype (blue) or mutated (red) CRLF2 protein, via activation of mutant (red) or wildtype (grey) JAK2 or other unknown kinases, as indicated.