Among them, 187 (92.1%) patients were positive for BCR-ABL fusion gene by RT-PCR and Philadelphia chromosome
on conventional cytogenetics (Figure-1).
Table-III: Simple and complex variants of Philadelphia chromosome
Valenti et al., "Chromosome abnormalities additional to the Philadelphia chromosome
at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications," Cancer Genetics and Cytogenetics, vol.
Initial work-up Baseline laboratory investigations FBC + differential Urea and electrolytes, liver enzymes, serum LDH, serum urate Pregnancy test BM aspirate and trephine biopsy for: Morphology, including differential count to determine phase of disease Assessment of fibrosis Cytogenetic assessment on BM to determine: * % Philadelphia-positive cells (preferably 20 metaphases) * Presence of variant Philadelphia chromosome
translocation * Presence of additional abnormalities, e.g.
It is the first disorder for which the term "leukemia" was used; the first malignancy associated with a recurring chromosomal abnormality (Philadelphia chromosome
); the first disease in which the chromosomal abnormality formed a fusion gene (BCR/ABL1 ); the first disease in which a protein fundamental to the pathogenesis of the disease was identified; and, the first disorder in which a therapeutic agent specifically targeted the molecular defect to effectively treat the disorder.
Dasatinib and nilotinib, alternate ABL kinase inhibitors, restore hematologic and cytogenetic remission in the majority of patients with primary failure or acquired resistance in chronic-phase disease; in advanced disease and Philadelphia chromosome
ALL, responses are more limited and relapse is common," Dr.
Most people with CML have an abnormal chromosome, known as the Philadelphia chromosome
, in which segments of chromosomes 9 and 22 are fused.
The oncogenic activity arises from a translocation error between chromosomes 9 and 22; the abnormality of chromosome 22 is known as the Philadelphia chromosome
Scientists have continued to hammer away at the so-called Philadelphia chromosome
, a shortened chromosome 22.
The result is an assay that may be quicker, more sensitive, and more reproducible than previous RT-PCR-based assays for the Philadelphia chromosome
(bcr/abl translocation) that use either cell lysates or isolated RNA.
The discovery of the Philadelphia chromosome
revolutionized the treatment of leukemia with the development of targeted tyrosine kinase inhibitors.