Translocation of c-abl to “Masked” Ph in chronic myeloid leukemia

Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML

“…A morphological evaluation is made of slides of peripheral blood smears, surgical biopsy specimens, bone marrow, and tissues obtained at autopsy.To document the involvement of EBV, we perform a battery of tests depending on the availability of samples. Antibody titers of IgM, IgG, and IgA isotypes against viral capsid antigen (VCA) [11,12], early antigen (EA) [13], and EBNA [14] are measured. We also have measured anti-EBNA titers by enzyme-linked immunosorbent assay {ELISA), using a synthetic EBNA peptide [15].…”

“…We also have measured anti-EBNA titers by enzyme-linked immunosorbent assay {ELISA), using a synthetic EBNA peptide [15]. We stain available tissue imprints for EBNA [14] and probe for EBV genome using Southern blots hybridized with a cocktail of EBV DNA probes (cosmid clones 301 99 and 302-23, provided by Beverly Griffin) in DNA extracted from cryopreserved tissues obtained at autopsy or from surgical biopsy specimens [16]. We have also performed immunoblotting studies to search for EBV-encoded proteins in extracts of tissues from 15 male patients who died of IM [17].…”

BCR translocation to derivative chromosome 2: a new case of chronic myeloid leukemia with a complex variant translocation and Philadelphia chromosome

“…Using conventional cytogenetic analysis, two variant subgroups have traditionally been identified: complex t(9;22;V) where V represents a third translocation partner chromosome, and simple t(9;V) or t(22;V) (6). Only a few cases exhibit a chromosomal fragment from the third chromosome translocated to the der(22)t(9;22) producing a 'masked Ph' (7). In the majority of Ph-variant cases, the segment 22q11-qter shifts to a third chromosome, while a part of the third chromosome is located on 9q34.…”

Insertion of the 3′ ABL region into the long arm of chromosome 1 in a Philadelphia chromosome-negative chronic myeloid leukemia case

“…In approximately 1% of CML patients, bone marrow cells appear to be Ph-negative by G-banding, although the BCR/ABL fusion gene can be identified by molecular means and can be located by fluorescence in situ hybridization (FISH) on chromosome 22q11, 9q34 or even a third chromosome (2)(3)(4)(5). Cases of Ph-negative BCR/ABL-positive CML with the chimeric gene present on derivative chromosome der(22), as in the majority of CML cases, or alternatively on der(9) appear to have the same clinical and molecular characteristics as Ph-positive patients.…”

“…The biology and clinical significance of genetic rearrangements in Ph-negative BCR/ABL-positive disease was evaluated following initial descriptions (2)(3)(4)(5). Two mechanisms involved in the formation of the chimeric gene in masked Ph-positive cells have been postulated: insertion of ABL into the BCR region (or vice versa), or by a multiple-step model where a classical t(9;22) is followed by translocation of the two products and/or another autosome, thereby restoring the normal chromosome morphology.…”