B-chronic lymphocytic leukemia chemoresistance involves innate and acquired leukemic side population cells

Gross, Emilie; Fe, L'Faqihi-Olive; Ysebaert, Loïc; Brassac, M; Struski, Stéphanie; Kheirallah, Samar; Jj, Fournié; Laurent, Guy; Quillet‐Mary, Anne

doi:10.1038/leu.2010.176

Cited by 18 publications

(17 citation statements)

References 37 publications

(51 reference statements)

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“…We previously described that CLL SP cells were insensitive to RTX-induced cytotoxicity. 5 Here no differences were observed between SP and non-SP cells in terms of BI 836826-induced B-cell depletion, suggesting that both populations were equally targeted by BI 836826 and that CD37 could be a better target to deplete CLL leukemic cells in vivo (Figure 1c). …”

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confidence: 91%

“…8, 9 SP cells experiments were done as previously described (Supplementary Information 3). 5, 10 Flow cytometric analysis revealed a higher CD37 expression in SP cells compared with its non-SP counterpart in CLL samples from relapsed patients (Figure 1a), suggesting that SP cells could be sensitive to BI 836826 cytotoxicity. The PBMC depletion assays were then performed in a large cohort ( n= 16) of relapsed CLL patients.…”

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confidence: 99%

“…Among chemo-resistant cells, side population (SP) cells have been reported in blood samples from CLL patients. 4, 5 SP cells appear resistant to conventional treatment including fludarabine, bendamustine and rituximab, and seem to be selected by these treatments. 4, 5 SP cells should be considered as relapse-initiating cells in the development of new therapeutic agents.…”

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confidence: 99%

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Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Bétrian

Ysebaert

Heider

et al. 2016

Blood Cancer Journal

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confidence: 91%

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confidence: 99%

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confidence: 99%

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Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Bétrian

Ysebaert

Heider

et al. 2016

Blood Cancer Journal

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“…These transporters can also exclude other agents from the cell, including cytotoxic agents. SP cells can be enhanced for their ability to exclude chemotherapeutic or other toxic agents and this property could make them resistant to certain therapies (46)(47)(48). SP cells could become resistant clones of tumor cells that are characteristic of neoplastic cells found in recurrent disease (49).…”

Section: Discussionmentioning

confidence: 99%

Hedgehog and Notch Signaling Regulate Self-Renewal of Undifferentiated Pleomorphic Sarcomas

et al. 2012

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Like many solid tumors, sarcomas are heterogeneous and include a small fraction of the so-called side population (SP) cells with stem-like tumor-initiating potential. Here, we report that SP cells from a soft tissue tumor of enigmatic origin termed undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma or MFH sarcoma) display activation of both the Hedgehog and Notch pathways. Blockade to these pathways in murine xenograft models, this human cancer decreased the proportion of SP cells present and suppressed tumor self-renewal, as illustrated by the striking inability of xenograft tumors subjected to pathway blockade to be serially transplanted to new hosts. In contrast, conventional chemotherapies increased the proportion of SP cells present in tumor xenografts and did not affect their ability to be serially transplanted. SP cells from these tumors displayed an unexpectedly high proliferation rate which was selectively inhibited by Hedgehog and Notch blockade compared with conventional chemotherapies. Together, our findings deepen the concept that Hedgehog and Notch signaling are fundamental drivers of tumor self-renewal, acting in a small population of tumor-initiating cells present in tumors. Furthermore, our results suggest not only novel treatment strategies for deadly recurrent unresectable forms of this soft tumor subtype, but also potential insights into its etiology which has been historically controversial. Cancer Res; 72(4); 1013-22. Ó2012 AACR.

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“…Matsui et al identified a MM clonogenic cell population, termed side population (SP), which had very active intracellular drug detoxification and efflux capacities conferring resistance to cyclophosphamide, dexamethasone, lenadilomide and bortezomib in vitro [70]. SP cells resistant to conventional drugs such as fludarabine, bendamustin and rituximab have also been identified in CLL [71]. Interestingly, SP cells could be transiently eliminated from the peripheral blood of CLL patients who received autologous hCD40L/IL-2 gene-modified tumor cells as part of a tumor vaccine study [72].…”

Section: Future Directionsmentioning

confidence: 99%

Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: from bench to bedside

Castella

Vitale

Coscia

et al. 2011

Cell. Mol. Life Sci.

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Many hematological malignancies consist of tumor cells that are spontaneously recognized and killed by Vγ9Vδ2 T cells. These tumor cells generate high amounts of intracellular phosphorylated metabolites mimicking the natural ligands and display a wide range of stress-induced self-ligands that are recognized by Vγ9Vδ2 T cells via TCR-dependent and TCR-independent mechanisms. The intrinsic features of Vγ9Vδ2 T cells and that of tumor cells of hematological origin constitute an ideal combination from which to develop Vγ9Vδ2 T cell-based immune interventions. In this review, we will discuss the rationale, preclinical and clinical data in favor of this therapeutic strategy and the future perspectives of its development.

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B-chronic lymphocytic leukemia chemoresistance involves innate and acquired leukemic side population cells

Cited by 18 publications

References 37 publications

Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Hedgehog and Notch Signaling Regulate Self-Renewal of Undifferentiated Pleomorphic Sarcomas

Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: from bench to bedside

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