Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations

Haase, D.; Feuring‐Buske, Michaela; Könemann, Stefan; Fonatsch, Christa; Troff, C.; Verbeek, Walter; Pekrun, Arnulf; Hiddemann, W.; Wörmann, Bernhard

doi:10.1182/blood.v86.8.2906.bloodjournal8682906

Cited by 30 publications

(35 citation statements)

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“…Tumor stem cells for myeloid leukemia, breast, lung, and brain cancers have been isolated and characterized. 1,[8][9][10][11][12][13][14][15][16][17][18][19] The question is whether stem cells cause therapeutic failure, and whether therapy should target resting stem cells or any resting cells for that matter.…”

Section: Introduction: What Is Actually the Question?mentioning

confidence: 99%

Target for cancer therapy: proliferating cells or stem cells

Mv¹

2005

Leukemia

172

117

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Tumor stem cells are quiescent and, therefore, resistant to therapy, yet harbor the capacity to replenish a tumor after therapy. Therefore, it is tempting to explain all therapeutic failures by the persistence of tumor stem cells. Yet, this explanation is relevant only to initial stages of stem-cell-dependent tumors (such as chronic myeloid leukemia) that, actually, are well controlled by therapy. In advanced cancers that poorly respond to therapy, quiescent tumor stem cells play a negligible role. Instead, proliferating cells determine disease progression, prognosis, therapeutic failures, and resistance to therapy. And therapy fails not because it eliminates only proliferating tumor cells, but because it does not eliminate them. With noticeable exceptions, it is the proliferating cell that should be targeted, whereas resting cancer cells including stem and dormant cells need to be targeted only when they 'wake up'. Finally, I discuss a strategy of selectively killing dominant proliferating clones, including proliferating stem-like and drug-resistant cancer cells, while sparing normal cells.

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Section: Introduction: What Is Actually the Question?mentioning

confidence: 99%

Target for cancer therapy: proliferating cells or stem cells

Mv¹

2005

Leukemia

172

117

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“…Molecular and cytogenetic abnormalities are major determinants in transforming normal CD 34 + cells to malignant cells in the bone marrow (BM) [16][17][18]. Cytogenetic analyses on hematological malignancies have identified various clonal chromosomal abnormalities in the haematopoeitic stem/ progenitors as well as in the myeloid and lymphoid lineages of blood cells [19][20][21][22][23][24]. However, the cell of origin of the cytogenetic abnormalities in MDS is still debatable.…”

Section: Introductionmentioning

confidence: 99%

The utility of hematopoietic stem cell karyotyping in the diagnosis of de novo myelodysplastic syndromes

2016

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Myelodysplastic syndromes (MDS) are a clonal hematopoietic stem cell (HSC) disorders. Cytogenetics plays a vital role in pathogenesis, diagnosis, prognosis, and determining treatments in MDS. Cytogenetic studies on CD 34 + cells in Asian MDS patients are limited. The aim of conducting this study was to compare the karyotypic features of CD 34 + cells and their bone marrow (BM) karyotypes. BM samples of 20 primary MDS patients were collected. BM-CD 34 + cells were isolated by CD34 positive selection. Conventional karyotyping was performed on primary BM samples and isolated CD 34 + cells. Fluorescence in situ hybridization (FISH) was performed to confirm del(5q) by using XL 5q31/5q33 locusspecific probe. Chromosomal abnormalities were detected in 41 % (7/17) of BM and 40 % (8/20) of HSC karyotypes. BM and HSC karyotypes were similar (94 %) except in one (BM-normal; CD 34+ cells had del(5q)) where the patient showed characteristic del(5q) phenotype. The abnormalities found were del(5q)-10 % (2/20), del(11q)-5 % (1/20), del(12p)-5 % (1/20), 47,XY,+19-5 % (1/20), hypodiploidy-5 % (1/20), and random loss of chromosomes-10 % (2/20). The percentage of abnormal metaphases counted per case was higher for CD 34 + cell cultures than for BM cultures. Culture failure were less for CD 34 + cells when compared to BM. Sample limitation for BM does not apply for CD 34 + cells if cultures can be maintained. Although the abnormal karyotypes counted were greater using CD 34 + cells than BM, there was no statistically significant difference (p > 0.05). Detection of karyotypic abnormalities could be greater when using CD 34 + cells. All the karyotypic abnormalities reported in this study had been previously known in MDS. Further large scale studies are needed to verify our findings.

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“…The acute leukemias are a heterogenous group of neoplasms arising from transformation of uncommitted or partially committed hematopoietic cells. 1 These are a malignant disorder of bone marrow in which maturational arrest in blood cell progenitors results in a failure of normal hematopoesis. Acute leukemias are currently classified pragmatically by combination of differentiation (acute myeloid leukemia versus acute lymphoid leukemia), pathogenesis (myelodysplasia related versus de nevo acute myleloid leukemia), and genetic abnormalities [e.g., acute promyelocytic leukemia with t (15;17)].…”

Section: Introductionmentioning

confidence: 99%