Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation

Ns, Lee; Hj, Cheong; Sj, Kim; Se, Kim; Ck, Kim; Kt, Lee; Sk, Park; Sh, Baick; Ds, Hong; Hs, Park; Jh, Won

doi:10.1038/sj.leu.2402960

Cited by 17 publications

(22 citation statements)

References 33 publications

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“…The contention that resting hematopoietic progenitors are not induced to apoptosis by TRAIL receptors [17][18][19][22][23][24] best describes the preservation of the engraftment and reconstituting potential, as shown here and in previous studies. 23 Humanmouse xenochimerism was not impaired by preincubation with TRAIL, showing that SCID-repopulating cells were spared and not induced into apoptosis.…”

Section: Discussionmentioning

confidence: 57%

“…20,21 Although mRNA encoding TRAIL receptors DR4 and DR5 is frequently detected in CD34 þ progenitors, these cells were insensitive to apoptosis 22,23 even in the presence of low doses of doxorubicin. 24 Consistently, infusion of soluble TRAIL into rodents was not associated with gross abnormalities in hematopoiesis, 25,26 and TRAIL neither induced nor impaired the clonogenic activity of human hematopoietic progenitors in vitro. 22,23 These data argue that TRAIL is not a significant factor in proximal stages of hematopoietic cell differentiation.…”

Section: Introductionmentioning

confidence: 58%

“…In general, our findings are consistent with previous reports showing that TRAIL does not negatively impact hematopoietic progenitors. 9,10,[22][23][24] However, detailed analysis of the dynamics of cultured cells revealed a complex pattern of cognate receptor induction, differential proliferation and sensitivity to apoptosis of cells expressing DR4 and DR5. In this study, we report that TRAIL induces expression of its two receptors involved in apoptotic signaling, triggers death of nonprogenitor UCB cells in culture and imposes both suppressive and inductive effects on clonogenic activity.…”

Section: Discussionmentioning

confidence: 99%

“…First, donor cells can be indeed purged of residual neoplastic cells if the latter are sensitive to TRAIL-induced apoptosis. 24 Second, activation of short-term reconstituting cells, corresponding to committed progenitors that are active in clonogenic assays, might augment early UCB cell engraftment, which is one of the problems associated with the use of this rich source of progenitors. 43 Third, overexpression of TRAIL in UCB-derived progenitors seems to be safe and might be of benefit.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11] Thus, in addition to the selective sensitivity of neoplastic cells to TRAIL, 2-4 its engraftment-promoting attributes suggest its usefulness as an immunotherapeutic adjuvant to chemotherapy. 24,44 Furthermore, membrane-bound ligands of the TNF family, such as Fas-ligand, are effective in counterattacking graft rejection in addition to graft supportive functions. 45 Therefore, TRAIL evolves as a promising immunotherapeutic agent, particularly in emerging approaches, to induce graft-versus-tumor reactivity through nonlife-threatening transplantation under nonmyeloablative conditioning.…”

Section: Discussionmentioning

confidence: 99%

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Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

et al. 2010

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The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway has selective toxicity to malignant cells. The TRAIL receptors DR4 and DR5 are expressed at low levels in human umbilical cord blood cells (3-15%) and are upregulated by incubation with the cognate ligand, triggering apoptosis in 70-80% of receptor-positive cells (Po0.001). Apoptosis is not induced in hematopoietic progenitors, as determined from sustained severe combined immunodeficiency reconstituting potential and clonogenic activity. Furthermore, elimination of dead cells after incubation with TRAIL for 72 h results in a threefold enrichment in myeloid progenitors. Exposure to TRAIL in semisolid cultures showed synergistic activity of DR4 and granulocyte/macrophage colony-stimulating factor in recruiting lineage-negative (lin À ) and CD34 þ progenitors and in promoting the formation of large colonies. In murine bone marrow, B30% of lin À cells express TRAIL-R2 (the only murine receptor), and the receptor is upregulated after transplantation in cycling and differentiating donor cells that home to the host marrow. However, this receptor is almost ubiquitously expressed in the most primitive (lin À SCA-1 þ c-kit þ ) progenitors, and stimulates the clonogenic activity of lin À cells (Po0.001), suggesting a tropic function after transplantation. It is concluded that TRAIL does not trigger apoptosis in hematopoietic progenitors, and upregulation of its cognate receptors under stress conditions mediates tropic signaling that supports recovery from hypoplasia.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

et al. 2010

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TNF‐α inhibitor etanercept and hematologic malignancies: Report of a case and review of the literature

2007

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We report here a 57-year-old man treated with etanercept for 6 months for psoriasis who developed myelodysplasia with acute myeloid leukemia. Leukemia cells had distinct karyotype associated with poor prognosis. The patient did not respond to cytosine arabinoside 100 mg/m 2 continuous infusion over 7 days with daunorubicin 45 mg/m 2 daily for 3 days. He also did not respond to salvage induction therapy with gemtuzumab (6 mg/m 2 on day 1 and 4 mg/m 2 on day 8) and intravenous continuous infusion cytosine arabinoside 200 mg/m 2 . We review other cases of lymphoma and leukemia associated with tumor necrosis factor inhibitors and suggest mechanisms by which inhibition of the TNF-a family may predispose to cancer. We also suggest that all patients being considered for TNF-a treatment be screened for hematologic malignancies or premalignancies with blood counts and bone marrow aspirates/biopsies if indicated. Am. J. Hematol. 82:1022Hematol. 82: -1024Hematol. 82: , 2007

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Emerging non‐apoptotic functions of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/Apo2L

Pietro

Zauli

2004

Journal Cellular Physiology

117

123

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Tumor necrosis factor (TNF) is a cytokine that mediates tumor necrosis. To date, 20 different members of the TNF super-family and 21 different receptors have been identified. All ligands of the TNF super-family have been found to activate transcription factor NF-kappa B and c-Jun kinase. Members of this family have diverse biological effects, including induction of apoptosis, promotion of cell survival, and regulation of the immune system and hematopoiesis. The current review focuses on the biological effects of TNF-related apoptosis-inducing ligand (TRAIL), a TNF super-family member which, a few years ago, generated considerable enthusiasm for its anticancer activity, not accompanied by general toxicity in most normal tissues and organs.

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Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation

Cited by 17 publications

References 33 publications

Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

TNF‐α inhibitor etanercept and hematologic malignancies: Report of a case and review of the literature

Emerging non‐apoptotic functions of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/Apo2L

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