e-abl Sequences in Ph-positive Acute Leukemias and Ph-negative CML - an Update
نویسنده
چکیده
The molecular hallmark of the Philadelphia (Ph) translocation in CML is a rearrangement between the e-abl oncogene and a gene provisionally called ber [7, 11, 13, 19]. As a consequence of this genomic recombination on the Ph chromosome, CML cells transcribe a chimeric 8.5-kb RNA species, consisting of both 5'ber and e-abl sequences [6, 10, 20], that is translated into a p 210 abl protein [15, 16]. As yet the normal cellular functions of e-abl and ber have not been characterized. However, e-abl belongs to a family of genes coding for proteins with associated tyrosine kinase activity; it is tempting to speculate that the ber moiety of the hybrid ber/abl molecule has altered the structure of the ablprotein and thus changed its tyrosine kinase activity. Recently, we extended the analyses of e-abl and ber sequences to Ph-negative CML and Ph-positive acute leukemias. The results are summarized below.
منابع مشابه
The INK4-ARF (CDKN2A/B) locus in hematopoiesis and BCR-ABL-induced leukemias.
Senescence and apoptosis programs governed by the Rb and p53 signaling networks can counter tissue stem cell self-renewal. A master regulator of Rb and p53 is the INK4-ARF (CDKN2A/B) locus that encodes two CDK inhibitors, p16(INK4A) and p15(INK4B), that maintain Rb in its active, hypophosphorylated form, and p14(ARF) (p19(Arf) in mice), that inhibits Mdm2 and activates p53. The INK4-ARF genes a...
متن کاملTreatment of Philadelphia positive (Ph+)ALL and CML in children
Philadelphia positive (Ph+) leukemias in children include essentially all chronic myeloid leukemias (CML) and 2% to 3% of childhood acute lymphoblastic leukemias (ALLs). Ph+ leukemias are characterized by a reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome). The translocation creates a fusion of human homologue of the Abelson Murine leukemia virus ABL on chromosome ...
متن کاملExpression of c-abl in Philadelphia-positive acute myelogenous leukemia.
The identical cytogenetic marker, t(9;22)(q34;q11) (Philadelphia [Ph] translocation), is found in approximately 90%, 20%, and 2% of adult patients with chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML), respectively. In CML, the molecular events resulting from the Ph translocation include a break within the bcr locus on chromosome 22, t...
متن کاملVariant breakpoint positions on chromosome 22 in Ph'-positive chronic myelogenous leukemias.
As a consequence of the molecular events associated with the presence of a Philadelphia (Ph') chromosome, two different types of abnormal c-abl proteins, termed P210 and P190 according to their molecular weight, have been found in Ph' positive leukemic cells [1, 2]. P210, expressed in almost all chronic myelogenous leukemias (CML) and in approximately half of the Ph' positive acute lymphoblasti...
متن کاملBCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome-positive leukemias.
It remains unresolved how different BCR-ABL transcripts differentially drive lymphoid and myeloid proliferation in Philadelphia chromosome-positive (Ph(+)) leukemias. We compared BCR-ABL transcript type and level with kinase domain (KD) mutation status, genotype, and phenotype in 1855 Ph(+) leukemias. Compared with e1a2/p190 BCR-ABL cases, de novo e13-e14a2/p210 Ph(+) lymphoid leukemia more fre...
متن کامل