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.
Hematologic, cytogenetic, and molecular studies demonstrated the heterogeneity of such cases, including the first example of clinically typical myelofibrosis (MF) associated with a bcr gene rearrangement characteristic of chronic myelogenous leukemia (CML).
Some reports in the recent literature have shown that the site of molecular rearrangement within the M-BCR area may have a prognostic value in Ph1 + CML patients.
We report a case of Ph1-positive, bcr-positive chronic myeloid leukemia blast crisis (CML-BC) which at presentation showed a mixed myeloid/B-lymphoid immunophenotype along with TdT positivity and, at the molecular level, an oligoclonal rearrangement of the immunoglobulin heavy chain (IgH) gene region.
The results suggest that a genomic insertion of 3' ABL into M-BCR in Ph-negative CML occurs by a single cytogenetic event rather than a two-translocation mechanism.
Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase.
Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis.
As demonstrated using a panel of somatic cell hybrids, the STMY3 gene is in band 22q11.2, in close proximity to the BCR gene involved in chronic myeloid leukemia, but far from the (11;22) translocation breakpoint observed in Ewing sarcoma.
Patients were evaluated pre-transplant, 30, 60, 90, and 180 days after BMT, and yearly thereafter for 1) the presence or absence of the Y chromosome in sex-mismatched allogeneic transplant recipients, 2) the presence or absence of the Philadelphia chromosome [t(9;22)] in patients transplanted for chronic myelogenous leukemia (CML), 3) restriction fragment length polymorphism (RFLP) profiles, and/or 4) clonal rearrangement of the bcr gene.
The first clear cut association of an oncogene with a specific cancer is the c-abl translocation in chronic myelogenous leukemia and acute lymphocytic leukemia; it has been observed in 90% of CML cases examined.
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.
Molecular biological studies on transforming genes in acute and chronic leukemia and the bcr gene in chronic myelocytic leukemia have been performed in exposed and non-exposed groups.
Molecular biologic studies on ras genes in acute and chronic leukemias and the bcr gene in chronic myelocytic leukemia were performed in exposed and non-exposed groups.
Analysis of the breakpoint cluster region (bcr) on chromosome 22 in the DNA of the affected cells (marrow) revealed evidence for one rearranged chromosome 22 and one normal chromosome 22, indicating that the t(15;22) was not due to the usual Ph translocation seen in CML.
We report a patient with chronic myeloid leukaemia (Philadelphia-positive with M-BCR rearrangement) in transformation whose blast cells had myelomonocytic morphology, absent terminal deoxynucleotidyl transferase expression and non-lymphoid cell surface markers (CD10-, CD19-, CD33+, CD14+, CD11+).
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.
Thirty-two cases of chronic myelogenous leukemia (CML) were studied to determine whether there was a correlation between the position of the chromosome breakpoint within the breakpoint cluster region (bcr) on chromosome 22 and the type of chimeric mRNA expression.