Acquired Cytogenetic Aberrations in Philadelphia Chromosome Negative Cells from Patients with Chronic Myelogenous Leukemia Not Associated with Definitive Myelodysplasia.
William W Bulkeley, Bijal Shah, Xiaohui Zhang, Javier Pinilla-Ibarz, Ling Zhang. University of South Florida College of Medicine, Tampa; Moffitt Cancer Center and Research Center, Tampa, FL
Background: Chromosome abnormalities in Philadelphia chromosome negative (Ph-) cells in patients with chronic myelogenous leukemia (CML) have been widely observed but the prognostic significance remains uncertain. The Ph- clone may occur before or after treatment of CML with tryrosine kinase inhibitors (TKIs). It is equivocal for the acquired clonal aberrations in ph- cells to be associated with secondary myelodysplastic syndrome (MDS). The study aims to observe the Ph- clonal evolution in CML correlated with peripheral blood and bone marrow findings.
Design: Cytogenetic reports by G-banding from patients with CML during 1/1999 to 12/09 at our institute were retrieved. Laboratory information and pathologic findings including bone marrow biopsy, FISH/PCR, and therapy are correlated. All available bone marrow slides from patients with cytopenia and additional chromosome aberrations in Ph- cells are reviewed by 2 pathologists to exclude myelodysplasia.
Results: Two hundreds and eight patients with CML are included. Fifteen patients developed acquired chromosomal abnormalities in Ph- cells solely or in addition to Ph+ cells during TKI treatment. Anemia was commonly observed. With the exception of 2 patients, leukocyte values were normal when no disease recurred or progressed. Seven of 16 patients showed mild or moderate megaloblastoid changes without other features of dyserythropoiesis. Of note, 9 occasions showed suppression or disappearance of the Ph- clone when they reacquired or increased Ph+ cells. General pathologic features are summarized in figure 1.
Conclusions: Trisomy 8, -7, -5q, -Y and other cytogenetic abnormalities in Ph- cells may be found in CML treated with TKIs. The findings are not diagnostic of secondary MDS albeit they may be accompanied by anemia and megaloblastoid changes. Recurrence or progression of Ph + CML clones may suppress Ph- clones. The exact role of these Ph- clonal aberrations in CML is worthy of further exploration.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 167, Monday Morning