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).
|Treatment||Number of Cases Tested||Cases with pseudo-Gaucher Cells||Pseudo-Gaucher cells+; bcr-abl+||Pseudo-Gaucher cells+; bcr-abl-|