Pseudo-Gaucher histiocytes identified up to 1 year after transplantation for CML are BCR/ABL-positive

Anastasi, John; Musvee, Tarannum; Roulston, Diane; Domer, Peter H.; Larson, Richard A.; Vardiman, James W.

doi:10.1038/sj.leu.2400900

Cited by 21 publications

(6 citation statements)

References 5 publications

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“…For this reason, PGCs retrieved after BMT were generated from the engrafted monocyte compartment of the donor, judging by their progeny. In contrast to an anecdotal report on two patients [3], in our series we found that postgraft recurrence of PGCs did not indicate CML or a leukaemic relapse, since cytogenetic and molecular-biological data failed to disclose a clonally transformed cell population. Considering the presence of PGCs in the pretreatment bone marrow in CML, the temporal reappearance of these specific cells in a significant number of patients immediately after BMT warrants explanation.…”

Section: Discussioncontrasting

confidence: 99%

“…Although a wealth of data has accumulated in recent decades on the occurrence of PCGs in CML [2,3,7,10,15,18,20,31,32,34], controversy and discussion still persist about their incidence, which has been reported to range between 20% and 70% [7]. Moreover, PCGs are not only observed in CML, but occasionally also in acute myeloid leukaemia (AML) and various reactive and congenital conditions [15], including thalassaemia [40] and dyserythropoietic anaemia type II [36].…”

Section: Discussionmentioning

confidence: 99%

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Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia

Thiele¹,

Kvasnicka²,

Beelen³

et al. 2000

Virchows Archiv

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A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express alpha-D-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40-50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9-45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia

Thiele¹,

Kvasnicka²,

Beelen³

et al. 2000

Virchows Archiv

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“…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.…”

contrasting

confidence: 77%

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

2014

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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...

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“…It has been postulated that this may reflect a persistent CML stem cell population that expresses high levels of BCR-ABL that allow it to circumvent the effects of imatinib inhibition. A less distressing possibility is that the transcript resides in a differentiated, nonproliferating cell compartment such as pseudo-Gaucher histiocytes [76]; however, a persistent CML stem cell appears more likely, as most patients even in CCR relapse following cessation of imatinib therapy. Nevertheless, the durability of MMR in most patients indicates that imatinib can keep this small residual CML population in a quiescent state with low likelihood of secondary resistance development and very low incidence of progression to advanced phase disease.…”

Section: Monitoring Algorithms To Detect Therapy Resistancementioning

confidence: 99%

Chronic Myelogenous Leukemia

Hasserjian

2009

Neoplastic Hematopathology

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Chronic myelogenous leukemia, BCR-ABL1+ (CML), is a myeloproliferative neoplasm defined by the presence of the BCR-ABL fusion gene produced by the t(9;22) (q32;q11) cytogenetic abnormality. CML manifests clinically as leukocytosis with circulating immature granulocytic precursors and splenomegaly. When untreated, its natural history is that of inexorable progression to an acute leukemia (blast crisis) after a prolonged chronic phase. The recent development of inhibitors of BCR-ABL tyrosine kinase activity have dramatically altered the clinical course of CML, with long-term remissions in most patients treated early in the course of disease.

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Pseudo-Gaucher histiocytes identified up to 1 year after transplantation for CML are BCR/ABL-positive

Cited by 21 publications

References 5 publications

Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia

Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia

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

Chronic Myelogenous Leukemia

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