Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies

Werner, Martin; Kaloutsi, V.; Buhr, T.; Delventhal, S.; Vykoupil, K. F.; Georgii, A.

doi:10.1007/bf01703443

Cited by 22 publications

(9 citation statements)

References 28 publications

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“…Conventional cytogenetics from bone marrow aspirates was performed according to standard protocols [27] and revealed normal diploid karyotypes in the five patients without evidence of neoplastic disease. Two patients with ANLL had trisomy 8 in 74% and 73%, respectively, and one patient with ANLL had monosomy 7 in 48% of the metaphases examined.…”

Section: Methodsmentioning

confidence: 99%

Detection of karyotype changes in interphase cells: oligonucleotide-primed in situ labelling versus fluorescence in situ hybridization

et al. 1997

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Interphase cytogenetics is a rapidly developing technique which is usually performed by fluorescence in situ hybridization (FISH). Recently, oligonucleotide-primed in situ synthesis (PRINS) has become established as a method of labelling centromeric regions of chromosomes in metaphase spreads. We tested the suitability of PRINS in detecting the exact copy number of chromosomes 1, 3, 7 and 8 in intact interphase cells of 17 cytological preparations derived from normal and neoplastic tissues. Control procedures consisted in preparation of metaphase spreads of lymphocytes of healthy donors, conventional cytogenetics in some of the specimens, and omission of the primers or Taq polymerase from the reaction mixture. All specimens were additionally examined by FISH and analysed blind by two experienced observers. Both PRINS and FISH revealed a corresponding distribution of hybridization signals for all chromosomes examined in specimens of normal bone marrow (n = 5), normal liver cells (n = 5), three samples of acute nonlymphocytic leukaemia in which conventional chromosome analyses had shown monosomy 7 or trisomy 8, and in four hepatocellular carcinomas that displayed trisomy 1. Overall, statistical analysis revealed no significant difference in the signal distribution between the two techniques. Our results demonstrate that PRINS is as reliable as FISH for detecting chromosome copy numbers in interphase nuclei of intact cells. The PRINS method, however, is easier to perform, faster and less expensive, holding great potential for future applications in diagnostic pathology.

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Section: Methodsmentioning

confidence: 99%

Detection of karyotype changes in interphase cells: oligonucleotide-primed in situ labelling versus fluorescence in situ hybridization

et al. 1997

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“…The bone marrow cells isolated from the buffy coats were cultured for 22 and 44 h, respectively, in RPMI medium (Gibco) supplemented with 15% fetal calf serum, the last hour in the presence of Colcemid (Serva). Chromosome preparation and banding analysis were done as described earlier [28].…”

Section: Methodsmentioning

confidence: 99%

Megakaryocytes carry the fused bcr-abl gene in chronic myeloid leukaemia: a fluorescence in situ hybridization analysis from bone marrow biopsies

Nolte

Werner

Ewig

et al. 1996

Vichows Archiv A Pathol Anat

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Histological examination of bone marrow biopsies shows that about one-third of chronic myeloid leukaemia (CML) patients exhibit an increase of megakaryocytes. The megakaryocytic predominance may be so striking that differentiation from other chronic myeloproliferative disorders (CMPD) may be difficult in some CML patients. Megakaryocytes in CML are clonal as demonstrated by loss of glucose-6-phosphate dehydrogenase isoenzymes. The Ph translocation, fusing the abl and bcr genes on chromosomes 9 and 22, however, obviously occurs as a second step in tumour development. So far, the Ph translocation has not been assigned explicitly to megakaryocytes. The question is whether the megakaryocytic cell lineage could harbour the bcr/abl fusion in those CML cases with striking proliferation of megakaryocytes but lack this genetic defect in cases with normal or decreased megakaryocyte counts. We therefore performed triple-colour fluorescence in situ hybridization (FISH) for portions of the bcr and abl genes flanking the breakpoint in CML in paraffin sections of CML cases with normal and with increased numbers of megakaryocytes. This method allows identification of the bcr/abl fusion in single, morphologically intact cells, whereas conventional cytogenetics requires lysis and thus destruction of the cell. Among the 21 CML patients examined by FISH, 10 were informative for bcr and abl genes and displayed distinct hybridization signals within nuclei of bone marrow cells. Besides the granulopoietic cells, megakaryocytes of all those patients (4 without and 6 with varying grades of megakaryocytic increase) displayed bcr/abl fusion signals indicative of a Ph translocation. The lack of hybridization signals in the remaining 11 cases indicates that this technique is not of value diagnostically and should be reserved for scientific questions. Positive controls consisted of conventional chromosome preparations from bone marrow aspirates demonstrating the Ph chromosome in all patients examined, and negative controls of paraffin sections of bone marrow biopsies from non-CML patients. These showed no fusion signals in bone marrow cells, including megakaryocytes, using FISH. Our results demonstrate clearly that not only the transforming event but also the Ph translocation leading to the bcr/abl fusion happens prior to the differentiation of the pluripotent stem cell into different myeloid lineages. The megakaryocytic proliferation evident in some CML cases is probably a consequence of the disease progress.

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“…Although very uncommon, such presentations in CML have been reported before. In an original observational study among 103 patients with CML, 8 correlating cytogenetics to bone marrow histopathology, the authors described 4 separate kinds of CML: common type, overlapping, megakaryocyte increase, and megakaryocyte predominance. Additional karyotypic abnormalities were detected in 8 of the 45 cases of the common type and 12 of the 42 cases with the latter 2 types.…”

Section: Case Presentationmentioning

confidence: 99%

An Unusual Case of Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia With Trisomy 19 Presenting With Megakaryoblastosis and Myelofibrosis

Aljinovic

Bogusz

Kantarci

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Initial identification of chronic myelogenous leukemia is very important since targeted therapy leads to life-saving remission. Rarely, chronic myelogenous leukemia presents with an unusual picture, making the diagnosis challenging. We describe such a case of chronic myelogenous leukemia in blast crisis in a previously healthy 61-year-old woman. The patient presented with fever, myalgias, and night sweats and was first worked up for an infectious etiology. Because of persistent anemia, a bone marrow biopsy was performed that revealed fibrosis with increased megakaryoblasts. Even though initial cytogenetic studies could not be performed because of "dry tap" aspirate, persistent efforts for cytogenetic studies were made, including a "squeeze preparation" from the core biopsy, which revealed t(9;22)(q34;q11.2) and trisomy 19. The patient was treated with tyrosine kinase inhibitors, chemotherapy, and subsequently an allogeneic stem cell transplant. She is in persistent remission. This case illustrates a complex presentation of chronic myelogenous leukemia and provides an overview of morphologic cues and the importance of performing cytogenetic studies that led to the diagnosis.

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Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies

Cited by 22 publications

References 28 publications

Detection of karyotype changes in interphase cells: oligonucleotide-primed in situ labelling versus fluorescence in situ hybridization

Detection of karyotype changes in interphase cells: oligonucleotide-primed in situ labelling versus fluorescence in situ hybridization

Megakaryocytes carry the fused bcr-abl gene in chronic myeloid leukaemia: a fluorescence in situ hybridization analysis from bone marrow biopsies

An Unusual Case of Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia With Trisomy 19 Presenting With Megakaryoblastosis and Myelofibrosis

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