Low‐molecular weight B cell growth factor (BCGF‐12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia

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Abstract
The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12‐kDa B cell growth factor (BCGF‐12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B‐CLL). First, recombinant BCGF‐12KD induced dose‐dependent DNA synthesis in neoplastic B cells of four B‐CLL patients tested. Second, seven different B‐CLL clones secreted a BCGF‐12KD‐like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF‐12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B‐CLL cells. Finally, BCGF‐12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B‐CLL cells (three of three patients). These findings strongly suggest that BCGF‐12KD can modulate the growth of B‐CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.