EXPRESSION OF A-MYB, BUT NOT C-MYB AND B-MYB, IS RESTRICTED TO BURKITTS-LYMPHOMA, SIG(-ACUTE LYMPHOBLASTIC-LEUKEMIA, AND A SUBSET OF CHRONIC LYMPHOCYTIC LEUKEMIAS() B)

The A-myb gene encodes a transcription factor that is related both fun ctionally and structurally to the v-myb oncogene. Following our observ ations that A-myb is expressed in a restricted subset of normal mature human B lymphocytes, with the phenotype CD38(+), CD39(-), slgM(-), we have now investigated the pattern of A-myb expression in neoplastic B cells representing the whole spectrum of B-cell differentiation and c ompared it to that of c-myb and B-myb. In a panel of 32 B-cell lines, A-myb was very strongly expressed in most Burkitt's lymphoma (BL) cell lines, but weak or negative in 2 pre-B acute lymphoblastic leukemia ( ALL), 4 non-Hodgkin's lymphoma (NHL), 6 Epstein-Barr virus-immortalize d lymphoblastoid cell lines, and 6 myeloma lines. Protein expression p aralleled that of the RNA. We have also investigated A-myb expression in 49 fresh cases of B leukemias. Among 24 ALL, 6 were of the null and 11 of the common type and all these were negative for A-myb expressio n; on the other hand, all 7 B-ALL cases (slg(+)), as well as one fresh BL case with bone marrow infiltration, expressed A-myb. A-myb was und etectable in 4 prolymphocytic leukemias (PLL) but was strongly express ed in 5/20 (25%) of chronic lymphocytic leukemia (CLL) samples, In the latter A-myb did not correlate with phenotype or clinical stage. Fina lly, we have studied the progression of one case of CLL into Richter's syndrome and have found that the Richter's cells expressed about 25-f old less A-myb RNA than the CLL cells from the same patient. The patte rn of c-myb and B-myb was clearly distinct from that of A-myb. C-myb a nd B-myb were expressed in all neoplastic groups, except in CLL cells. Thus, A-myb expression, unlike that of c-myb and B-myb, is restricted to a subset of B-cell neoplasias (in particular BL and slg(+)B-ALL) r epresentative of a specific stage of B-cell differentiation. This expr ession may in part reflect expression of A-myb by the normal germinal center B cells that are the normal counterpart of these transformed B cells, The data presented strongly support a role for this transcripti on factor in B-cell differentiation and perhaps in B-cell transformati on in some neoplasias. (C) 1996 by The American Society of Hematology.