IN-VITRO TRANSFORMATION OF MURINE PRO-B AND PRE-B CELLS BY V-MPL, A TRUNCATED FORM OF A CYTOKINE RECEPTOR

v-mpl is a constitutively activated, truncated form of a cytokine rece ptor that has been transduced in a murine retrovirus, the myeloprolife rative leukemia virus (MPLV). Expression of this oncogene results in t he factor-independent proliferation of myeloid, erythroid, megakaryocy tic, and mast precursor cells, which retain the ability to differentia te. However, no lymphoid disease was ever reported. To determine wheth er MPLV could infect and transform very early B cells and their precur sors (BCPs), lymphoid long-term bone marrow cultures were infected wit h a helper-free MPLV. Within 3 wk after infection, highly proliferatin g BCPs could be isolated. These cells were able to clone spontaneously in semi-solid cultures, grown in the absence of feeder cell layer or exogenous growth factor and rapidly produced tumors after s.c. injecti on into syngenic irradiated mice. In addition, MPLV transformation of pre-B cells led to the induction of an autocrine activity. Immunopheno typic and molecular analysis indicated that MPLV transformed early pro -B, pro-B, and pre-B cells, according to the expression of HSA, CD43, B220, Thy1, s-IgM and BP1 Ags, and to the rearrangements of Ig genes. Interestingly, MPLV-transformed BCPs expressed Mac1 Ag without acquiri ng further characteristics of macrophagic differentiation. Although th e v-mpl cytoplasmic domain is devoid of tyrosine kinase consensus sequ ence, MPLV-transformed pre-B cells contained a major similar to 105-kD a tyrosine-phosphorylated protein that was not detected in uninfected cells or in cells transformed by the Abelson viral oncogene (v-abl). T hese results demonstrate that, like v-abl, the truncated cytokine rece ptor v-mpl is able to transform BCPs in vitro and suggest that the onc ogenic transformation of BCPs by either v-mpl v-abl use different path ways.