Characterization of acute lymphoblastic leukemia progenitor cells

Cox, Charlotte V.; Evely, Roger S.; Oakhill, A.; Pamphilon, Derwood; Goulden, Nicholas; Blair, Allison

doi:10.1182/blood-2004-03-0901

Cited by 214 publications

(163 citation statements)

References 32 publications

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“…In addition, it was suggested that ETV6-RUNX1-positive cells capable of reconstituting leukemia upon transplantation to NOD-SCID mice have the CD19 À phenotype. 32 The inhibition of B-ALL cell spreading is likely related to the ability of IL-27 to function directly against tumor cell through inhibition of cell proliferation and angiogenesis, and induction of apoptosis, as supported by our in vitro results. Furthermore, we showed that IL-27 downregulated miR-155 in B-ALL cells.…”

Section: Discussionsupporting

confidence: 67%

Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

et al. 2011

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Section: Discussionsupporting

confidence: 67%

Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

et al. 2011

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“…These data indicate that primitive progenitor cells rather than more committed lymphoid cells are targeted by BCR-ABL gene rearrangement in ALL. A different study used human leukemic cells from patients with other subgroups of ALL 47,48 . ALL cells with a CD34+ CD10-phenotype were capable of transferring leukemia to NOD/SCID mice.…”

Section: Hematopoietic Stem Cells As Targets Of Transforming Mutationmentioning

confidence: 99%

Somatic stem cells and the origin of cancer

2006

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647Most human cancers derive from a single cell targeted by genetic and epigenetic alterations that initiate malignant transformation. Progressively, these early cancer cells give rise to different generations of daughter cells that accumulate additional mutations, acting in concert to drive the full neoplastic phenotype 1,2 . As we have currently deciphered many of the gene pathways disrupted in cancer, our knowledge about the nature of the normal cells susceptible to transformation upon mutation has remained more elusive. Adult stem cells are those that show long-term replicative potential, together with the capacities of self-renewal and multi-lineage differentiation. These stem cell properties are tightly regulated in normal development, yet their alteration may be a critical issue for tumorigenesis. This concept has arisen from the striking degree of similarity noted between somatic stem cells and cancer cells, including the fundamental abilities to self-renew and differentiate. Given these shared attributes, it has been proposed that cancers are caused by transforming mutations occurring in tissue-specific stem cells 3-9 . This hypothesis has been functionally supported by the observation that among all cancer cells within a particular tumor, only a minute cell fraction has the exclusive potential to regenerate the entire tumor cell population 3,10-13 ; these cells with stem-like properties have been termed cancer stem cells. Cancer stem cells can originate from mutation in normal somatic stem cells that deregulate their physiological programs. Alternatively, mutations may target more committed progenitor cells or even mature cells, which become reprogrammed to acquire stem-like functions 14,15 In any case, mutated genes should promote expansion of stem/progenitor cells, thus increasing their predisposition to cancer development by expanding self-renewal and pluripotency over their normal tendency towards relative quiescency and proper differentiation.

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“…However, in the acute leukaemic phase of CML or in P190-B-ALL, imatinib treatment is not effective (Shah et al, 2002). The origin of CML and p190-B-ALL begins in a haematopoietic stem cell (HSC), a target population that is largely quiescent (Cobaleda et al, 2000;Cox et al, 2004). In vitro and in vivo studies in the last years have shown that these quiescent Ph þ HSCs are insensitive to imatinib mesylate treatment (Graham et al, 2002;Chu et al, 2005) and these cells have not been eliminated in Ph þ patients.…”

Section: Introductionmentioning

confidence: 99%

Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice

et al. 2006

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Pharmacological inactivation of cancer genes or products is being used as a strategy for therapy in oncology. To investigate the potential role of BCR-ABLp190 cessation in leukaemia development, we generated mice carrying a tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically normal at birth, and developed leukaemias. Disease was characterized by the presence of B-cell blasts co-expressing myeloid markers, reminiscent of the human counterpart. BCR-ABLp190 activation can initiate leukaemia in both young and adult mice. Transitory expression of BCR-ABLp190 is enough to develop leukaemia. Suppression of the BCR-ABLp190 transgene in leukaemic CombitTA-p190 mice did not rescue the malignant phenotype, indicating that BCRABLp190 is not required to maintain the disease in mice. Similar results were obtained by inactivation of BCRABLp190 with STI571 (Gleevec; Novartis, East Hanover, NJ, USA) in leukaemic CombitTA-p190 mice. However, gradual suppression of BCR-ABLp190 in leukaemic CombitTA-p190 mice identified a minimum level of BCR-ABLp190 expression necessary to revert the specific block in B-cell differentiation in the leukaemic cells. Overall, the findings indicate that BCR-ABLp190 appears to cause epigenetic and/or genetic changes in tumourmaintaining cells that render them insensitive to BCRABLp190 inactivation.

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Characterization of acute lymphoblastic leukemia progenitor cells

Cited by 214 publications

References 32 publications

Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

Somatic stem cells and the origin of cancer

Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice

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