Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-...

Cancer is driven by a selection for mutations that include single nucleotide substitutions, short indels, and large-scale rearrangements of the genome [e.g., chromosomal inversions, translocations, segmental deletions, segmental duplications, and changes in chromosome copy number (aneuploidy and polyploidy)]. The frequency of these events varies greatly among tumors. For example, some tumors ex...

W e have previously shown that the chimeric gene ABLBCR, formed on the derivative chromosome 9q + as a result of the t(9;22) translocation, is transcriptionally active in 65% of chronic myeloid leukemia patients. W e have now used the same technique, reverse transcription/polymerase chain reaction amplification of ABL-BCR transcripts, to study nine patients with Philadelphia (Ph) chromosome-pos...

Chronic myelogenous leukemia (CML) results from a t(9,22) translocation, producing the p210(BCR-ABL) oncoprotein, a tyrosine kinase that causes transformation and chemotherapy resistance. To further understand mechanisms mediating chemotherapy resistance, we identified 556 differentially regulated genes in HL-60 cells stably expressing p210(BCR-ABL) versus those expressing an empty vector using...

Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromosome. which results from a reciprocal translocation between chromosomes 9 and 22. This activates the abi oncogene by moving it from chromosome 9 and combining it with sequence located on chromosome 22. The new fusion gene. with chromosome 22 sequence at its 5’ end and chromosome 9-abl sequence at its 3’ end. gener...

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to le...

The reciprocal translocation between chromosomes 9 and 22 that fuses coding sequences of the Bcr and Abl genes is responsible for a remarkably diverse group of hematologic malignancies. A newly described 230-kd form of Bcr-Abl has been associated with an indolent myeloproliferative syndrome referred to as chronic neutrophilic leukemia. We have cloned the corresponding gene and examined the biol...

The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, we have developed a method of amplifying and detecting only ...

Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by the excessive proliferation of the myeloid lineage. In its initial chronic phase, the myeloid progenitor cells expand and demonstrate apparently normal differentiation. The disease may then transform into the accelerated phase, usually associated with resistance to therapy, and finally, into acute leukemic pro...

The real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) has become the method of choice for the quantification of specific mRNAs. This method is fast, extremely sensitive, and accurate, requires only very small amounts of input RNA, and is relatively simple to perform. These characteristics have made it the method of choice for minimal residual disease monitoring suc...