Aggregates of pseudo-Gaucher cells after treatment of chronic myeloid leukemia in blastic phase

Abstract

induction chemotherapy consisting of DA regimen (daunorubicin 60 mg/m 2 for three days and cytarabine 200 mg/ m 2 for seven days) together with tyrosine kinase inhibitor imatinib (Glivec, Novartis) at 800 mg daily. This therapy was well tolerated and no serious events were noted during her treatment. WBC count returned to normal and no immature cells were detected in blood smear after therapy. Her repeated bone marrow aspirate included less than 5 % of myeloblasts; however, the aggregates of pseudo-Gaucher cells (PGC) were seen within the marrow (Fig. 1). PGC were found to be monocyte-derived and their immunochemistry was as follows: CD14 + , CD15 − , CD20 − , CD23 − , CD31 + , CD38 − , CD68 + , CD163 + , MPO − . The rereview of BM aspirate and biopsy from diagnosis did not reveal the presence of PGC. At follow-up visit, the Philadelphia chromosome was not detected on routine cytogenetic study. These cells did not possess BCR-ABL1 on FISH study, but the two BCR-ABL1 transcripts (p210 and p190) were still detected by quantitative (Q)-PCR (0.9 and 0.1 %, respectively). As the FISH method is significantly less sensitive than Q-PCR, the lack of similarity of results is unsurprising.A single study has previously shown that PGC found in CML may carry BCR-ABL1 fusion [1]. In contrast, we were unable to determine their clonal origin in our case.The morphology of these cells is identical to those seen in the hereditary form of Gaucher's disease (GD), but the pathogenesis is different. Namely, the activity of the enzyme glucocerebrosidase was found to be decreased in GD. Conversely, its activity was elevated in the acquired form seen in CML. Thus, the accumulation of glucocerebroside in CML may result from markedly increased granulocyte turnover followed by overproduction of glucocerebrosidase which is ultimately insufficient to metabolize the glucocerebroside [2].A 43-year-old previously healthy female was admitted to our hematology unit with suspicion of myeloproliferative neoplasm. She had a 2-week history of fever and cough unresponsive to antibiotics. Her white blood cell (WBC) count was extremely high (118 × 10 9 /L), whereas hemoglobin concentration and platelet count were within the normal range (11.8 g/dL and 194 × 10 9 /L, respectively). Blood differential was as follows: myeloblasts: 47 %, promyelocytes: 12 %, myelocytes: 2 %, metamyelocytes: 2 %, bands: 4 %, segmented: 20 %, eosinophils: 3 %, basophils: 8 % and monocytes: 2 %. Biochemistry was normal. A massive splenomegaly (20 cm) was found on abdominal ultrasound. Bone marrow (BM) analysis revealed a predominance of granulocytic line with >50 % of blast cells which were found to be of myeloid origin by flow cytometry. Cytogenetic examination detected a complex karyotype with duplication of Philadelphia chromosome: 47, XX, t(7;8)(q31;q12), t(9;22)(q34;q11), +der(22), t(9;22) (q34;q11). Reverse-transcription-polymerase chain reaction (RT-PCR) study detected the presence of two BCR-ABL1 transcripts: p210 and p190. There was no mutation in the ABL domain. The pat...

Aggregates of Pseudogaucher Cells in a Pediatric Patient With Chronic Myeloid Leukemia

“…PGC are composed from the accumulation of leukocyte membrane derived glucocerebroside inside macrophages. 2,3 By morphology PCG are indistinguishable from true Gaucher cells. Iron staining and electron microscopy may be useful to distinguish them, being especially helpful in cases were the presence of PGC is not expected.…”

“…PCG are histiocytes with rounded contour and deep blue cytoplasm resembling “onion layers.” PGC are composed from the accumulation of leukocyte membrane derived glucocerebroside inside macrophages 2,3. By morphology PCG are indistinguishable from true Gaucher cells.…”

“…Although PGC are frequently observed in CML, large aggregates in bone marrow smear are uncommon 4. In pretyrosine kinase era, PGC were related with better outcome 2,3…”