[1415] Pseudo-Gaucher Cells Are a Persistent Morphologic Biomarker of CML in the Bone Marrow of Patients Treated with TKIs Despite the Absence of Detectable Bcr-abl Transcript

O Pozdnyakova, SJ Rodig. Brigham and Women's Hospital, Boston, MA

Background: Pseudo-Gaucher cells (sea-blue histiocytes) that harbor the t(9;22) are a characteristic feature of the bone marrow microenvironment in patients presenting with chronic phase CML. Furthermore, both Philadelphia-chromosome positive (Ph+) pseudo-Gaucher cells and bcr-abl transcript are detectable for up to one year in patients in clinical remission following bone marrow transplant. We have observed persistent pseudo-Gaucher cells in the bone marrows of a subset of patients with CML treated with tyrosine kinase inhibitors (TKIs) and in clinical and cytogenetic remission. We sought to determine whether these cells predict the detection of bcr-abl transcript by molecular analysis.
Design: We surveyed 380 Giemsa-stained bone marrow biopsies and/or aspirate smears from a total of 78 patients with chronic phase CML in hematologic and cytogenetic remission following treatment with a TKI. In 119 cases, the findings were correlated with quantitative RT-PCR analysis of aspirate material for bcr-abl transcript levels.
Results: We found that 234 of 380 biopsies and/or aspirates (62%) contained pseudo-Gaucher cells. These cases included patients treated with all three major TKIs. In 78 of 119 cases (66%) the presence of pseudo-Gaucher cells correlated with the detection of bcr-abl transcript by RT-PCR analysis. However in 41 of 119 cases (34%), pseudo-Gaucher cells were observed in the absence of detectable bcr-abl transcript. Among those without detectable transcript, pseudo-Gaucher cells persisted in serial bone marrow biopsies for an average of 3.6 years (range 0.5-9 years).

Correlation of the presence of pseudo-Gaucher cells with the detection of bcr-abl transcript
TreatmentNumber of Cases TestedCases with pseudo-Gaucher CellsPseudo-Gaucher cells+; bcr-abl+Pseudo-Gaucher cells+; bcr-abl-
Imatinib3112136237
Dasatinib4113103
Nilotinib28861
Total3802347841



Conclusions: Pseudo-Gaucher cells are a morphologic biomarker of CML that often persists in the bone marrow of patients treated with TKIs. However the continued presence of pseudo-Gaucher cells does not imply continued detection of bcr-abl transcript by RT-PCR analysis. In contrast to the Ph+ pseudo-Gaucher cells that are characteristic of untreated CML, our findings suggest a selection for Ph- pseudo-Gaucher cells following TKI treatment. Cell-specific FISH analysis is ongoing in order to establish whether there are genetic differences between pseudo-Gaucher cells prior to, and after TKI treatment.
Category: Hematopathology

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 195, Wednesday Afternoon

 

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