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CCAAT enhancer-binding protein (CEBP) transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPA are found in a subset of acute myeloid leukemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH), and molecular cloning, we show that 5 CEBP gene family members are targeted by recurrent IGH chromosomal translocations in BCP-ALL. Ten patients with t(8;14)(q11;q32) involved CEBPD on chromosome 8, and 9 patients with t(14;19)(q32;q13) involved CEBPA, while a further patient involved CEBPG, located 71 kb telomeric of CEBPA in chromosome band 19q13; 4 patients with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPE and 3 patients with t(14;20)(q32;q13) involved CEBPB. In 16 patients the translocation breakpoints were cloned using long-distance inverse–polymerase chain reaction (LDI-PCR). With the exception of CEBPD breakpoints, which were scattered within a 43-kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5′ or 3′ of the involved CEBP gene. Except in 1 patient with t(14;14)(q11;q32), the involved CEBP genes retained germ-line sequences. Quantitative reverse transcription (RT)–PCR showed overexpression of the translocated CEBP gene. Our findings implicate the CEBP gene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBP dysregulation in myeloid and lymphoid leukemogenesis.

CCAAT enhancer-binding protein (CEBP)transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPAare found in a subset of acute myeloid leukemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH), and molecular cloning, we show that 5 CEBPgene family members are targeted by recurrent IGHchromosomal translocations in BCP-ALL. Ten patients with t(8;14)(q11;q32) involved CEBPDon chromosome 8, and 9 patients with t(14;19)(q32;q13) involved CEBPA, while a further patient involved CEBPG, located 71 kb telomeric of CEBPAin chromosome band 19q13; 4 patients with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPEand 3 patients with t(14;20)(q32;q13) involved CEBPB. In 16 patients the translocation breakpoints were cloned using long-distance inverse–polymerase chain reaction (LDI-PCR). With the exception of CEBPDbreakpoints, which were scattered within a 43-kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5′ or 3′ of the involved CEBPgene. Except in 1 patient with t(14;14)(q11;q32), the involved CEBPgenes retained germ-line sequences. Quantitative reverse transcription (RT)–PCR showed overexpression of the translocated CEBPgene. Our findings implicate the CEBPgene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBPdysregulation in myeloid and lymphoid leukemogenesis.

The localization of cellular oncogenes near the break points of tumour-specific chromosomal aberrations suggests an involvement of these genes in the generation of neoplasms1,2. Recently, we demonstrated3the translocation of the human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) from chromosome 9 to the Philadelphia chromosome (Ph1) in chronic myelocytic leukaemia (CML). In an attempt to investigate the significance of this translocation in the pathogenesis of CML, we have now studied two CML patients with complex translations, t(9; 11; 22) and t(1; 9; 22), and two CML Ph1-negative patients with apparently normal karyotypes. In addition to using blot hybridization with human c-abl probes and DNA from Rodent: CML cell hybrids as before, we have used in situ hybridization of these probes directly to metaphase chromosomes of CML patients. These studies show that the c-abl gene is translocated in Ph1-positive but not in Ph1-negative CML patients. CML without the Ph1chromosome seems to be a distince entity with a different origin, and this view is supported by clinical observations including correlations which reveal a poorer prognosis4,5.

Research into the effects of low levels of SO2on grasses has revealed no direct correlation between the dose of this pollutant and the plant's response1. Authors have suggested that environmental factors are of prime importance in the control of the response, because in many cases damage was most severe during the winter2,3. I have investigated the influence of total irradiance on the sensitivity of grasses to SO2, and shown that the effect of the pollutant was greatest in conditions of low irradiance and short photoperiod. Together, these factors may contribute to the increased sensitivity of plants during winter exposures to pollutants.