High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia

Aberrant proliferation, differentiation, and/or migration of progenitors ob served in various hematological malignancies may be caused by defects in ex pression and/or function of integrins. In this study, we have developed a n ew fluorescent beads adhesion assay that facilitates flow cytometric invest igation of lymphocyte function-associated antigen 1 (LFA-1)and very late ac tivation antigen-4 (VLA-l)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cel l population within one blood or bone marrow sample. Surprisingly, of the 2 0 B-lineage ALL patients investigated, 17 contained a leukemic cell populat ion with LFA-1- and/or VLA-4-mediated adhesion defects. Five patients conta ined CD10(+) cells that did not exhibit any LFA-1-mediated adhesion due to the lack of LFA-1 surface expression. The CD10(+) cells from 10 ALL patient s expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 18 acetate (PMA), whereas the CD10(-) cells expressed a functi onal LFA-1, Seven patients contained CD10(+) cells that expressed a PMA-unr esponsive form of VLA-4, The PMA unresponsiveness of the integrins LFA-1 an d VLA-1 expressed by the CD10(+) cells may be due to mutations in the integ rins itself, in protein kinases, or in other intracellular molecules involv ed in integrin adhesion. These data clearly demonstrate the importance of i nvestigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could sugges t a causal relationship between integrin mediated adhesion and B-lineage AL L. (C) 1999 by The American Society of Hematology.