title: Expression of A-myb, but not c-myb and B-myb, is restricted to Burkitt's lymphoma, sIg+ B-acute lymphoblastic leukemia, and a subset of chronic lymphocytic leukemias.
abstract: The A-myb gene encodes a transcription factor that is related both functionally and structurally to the v-myb oncogene. Following our observations 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 representating the whole spectrum of B-cell differentiation and compared 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-immortalized lymphoblastoid cell lines, and 6 myeloma lines. Protein expression paralleled 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 expression; 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 undetectable in 4 prolymphocytic leukemias (PLL) but was strongly expressed in 5/20 (25%) of chronic lymphocytic leukemia (CLL) samples. In the latter A-myb did not correlate with phenotype or clinical stage. Finally, 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-fold less A-myb RNA than the CLL cells from the same patient. The pattern of c-myb and B-myb was clearly distinct from that of A-myb. C-myb and 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) representative of a specific stage of B-cell differentiation. This expression 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 transcription factor in B-cell differentiation and perhaps in B-cell transformation in some neoplasias.
authors.affiliation: Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Golay
authors.forename: M
authors.initials: M
authors.lastname: Luppi
authors.forename: S
authors.initials: S
authors.lastname: Songia
authors.forename: C
authors.initials: C
authors.lastname: Palvarini
authors.forename: L
authors.initials: L
authors.lastname: Lombardi
authors.forename: A
authors.initials: A
authors.lastname: Aiello
authors.forename: D
authors.initials: D
authors.lastname: Delia
authors.forename: K
authors.initials: K
authors.lastname: Lam
authors.forename: D H
authors.initials: DH
authors.lastname: Crawford
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: T
authors.initials: T
authors.lastname: Barbui
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.forename: M
authors.initials: M
authors.lastname: Introna
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002051:Burkitt Lymphoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D054278:Embryonal Carcinoma Stem Cells; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D013577:Syndrome; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088831:MYBL1 protein, human; C064352:MYBL2 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012334:RNA, Neoplasm; D015534:Trans-Activators; D014157:Transcription Factors