We therefore sought evidence for analogous point mutations in the ABL gene in patients with Ph-negative, BCR-negative CML (n = 25), Ph-negative ALL (n = 18) and in Ph-positive CML in transformation (n = 28).
The hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome (Ph1) which is caused by a translocation of the c-abl gene from chromosome 9 to the breakpoint cluster region (bcr) on chromosome 22.
The cytogenetic hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome (Ph1), which reflects a chromosomal translocation t(9;22) and a rearrangement of the ABL and bcr genes.
In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis.
Meanwhile, the rearranged 3'-bcr fragments showed comigration with rearranged pHabl5' (or T39-1-2) fragments in all patients with Ph-positive CML, indicating the linkage of the 5' end of ABL to the 3' part of M-BCR on 9q+ chromosome.
In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR-ABL transcripts.
We used polymerase chain reaction to amplify the chimeric BCR-ABL transcripts in 18 patients with chronic myelogenous leukemia who became Ph1 chromosome negative while receiving treatment with interferon-alpha, either alone or in combination with interferon-gamma.
The NarI restriction sites are very close to the BssHII sites in the BCR gene, but they differ in the ABL gene, so that NarI digests could theoretically provide additional information in chronic myeloid leukaemia (CML) patients.
The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML).
Molecular studies by Southern and PCR analyses showed the rearrangement of the BCR and ABL sequences and expression of the chimeric bcr/abl mRNA, thus confirming the diagnosis of CML.
The 18-mer antisense directed against the specific BCR/ABL mRNA breakpoint region diminished the colony formation by CML-CP and CML-BC cells, but not by NBMC.
Clinical significance of bcr-abl gene rearrangement detected by polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia.
To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions.
In Philadelphia chromosome (Ph1) positive chronic myeloid leukemia (CML) the bcr and c-abl genes are reorganized and a new transcript, composed of both genes is expressed.
Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation.
Leukemia cells from adults with Philadelphia (Ph1)-chromosome positive chronic myelogenous leukemia (CML) have a characteristic molecular rearrangement between the BCR and ABL genes whereby major breakpoint cluster region (Mbcr) exons 2 or 3 are joined to ABL exon II.
These studies indicate that Southern hybridization analysis combined with the polymerase chain reaction assay is a useful approach to understanding the pathologic role of bcr-abl gene recombination and expression in the development of CML.
These results do not support the existence of BCR-ABL induced autocrine or paracrine mechanisms in CML and suggest that constitutive activation of events normally dependent on growth factor receptor stimulation is more likely to underlie the lack of proliferation control exhibited by primitive Ph1-positive cells.
The high degree of heterogeneity in the site of the breakpoint within zone 3 of the M-bcr, combined with the type of BCR-ABL hybrid mRNA expressed, further implicates BCR exon b3 in the pathogenesis of CML.