Pharmacological inhibition of EGFR signaling enhances G-CSF–induced hematopoietic stem cell mobilization

Ryan, Marnie A.; Nattamai, Kalpana; Xing, Ellen; Schleimer, David; Daria, Deidre; Sengupta, Amitava; Köhler, Annette G.; Liu, Wei; Gunzer, Matthias; Jansen, Michael; Ratner, Nancy; Cras, Timothy D. Le; Waterstrat, Amanda; Zant, Gary Van; Cancelas, José A.; Zheng, Yi; Geiger, Hartmut

doi:10.1038/nm.2217

Cited by 60 publications

(55 citation statements)

References 40 publications

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“…Cytokine receptors are widely expressed in various cells, which can receive cytokine (such as G-CSF) stimulation and initiate certain cellular responses. 20 In Figure 1b, the ELISA assays of plasma TRAIL levels in G-CSF-mobilized donors were slightly decreased, but the change was not statistically significant (P ¼ 0.058). Although the level of TRAIL did not change significantly, the cytotoxicity of NK cells was decreased by G-CSF in this study and in our previous study.…”

Section: Discussionmentioning

confidence: 93%

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

et al. 2011

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 93%

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

et al. 2011

Bone Marrow Transplant

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“…105,106 The mechanisms could involve qualitative and quantitative differences in HSCs in the BM, a difference in how HSCs migrate, and how the niches are down-regulated in response to G-CSF. 107 These genetic approaches have identified the epidermal growth factor receptor pathway and the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib as an adjuvant treatment to enhance mobilization in response to G-CSF in poorly responding mouse strains, 107 although no human data are available. Genetic polymorphism analyses in humans have identified polymorphisms associated with mobilizing response to G-CSF in untranslated regulatory regions of genes encoding GCSFR, adhesion molecules (VCAM-1, CD44), and chemokines (SDF-1), which are all known to regulate HSC trafficking.…”

Section: Age-related Poor Mobilizationmentioning

confidence: 99%

How I treat patients who mobilize hematopoietic stem cells poorly

Levesque

Herbert

2011

Blood

206

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Transplantation with 2-5 ؋ 10 6 mobilized CD34 ؉ cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established.To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify IntroductionHematopoietic stem cell transplantation (HSCT) has revolutionized the curative approach to a number of malignancies and BM failure syndromes by providing hematopoietic and immune rescue after high-dose cytoreductive therapy and, in allogeneic transplantations, graft-versus-tumor effect. [1][2][3][4] The term "mobilization" was first used to describe a 4-fold increase of circulating myeloid progenitors (granulocyte macrophage CFU [CFU-GM]) after the administration of endotoxin to healthy volunteers in 1977. 5 High levels of CFU-GM after recovery from myelosuppressive chemotherapy in humans was first described in 1976. 6 However, it was not until the 1980s that the use of chemotherapy-mobilized HSCs for transplantation was established. [7][8][9] Subsequently, a single high-dose cyclophosphamide was developed as a generic mobilizer. 10 Prof Metcalf led the study that showed the potential of G-CSF in mobilization. 11 Subsequently, 2 Australian centers in Melbourne and Adelaide showed for the first time the use of G-CSF-mobilized HSCs for transplantation, 12 and reports of combined G-CSF and chemotherapy mobilization soon followed. 13 Now, virtually all autologous and three-quarters of allogeneic transplantations are performed with mobilized HSCs (CIBMTR reports). 14,15 The cell dose effect of HSCT describes a threshold of HSCs that, when transplanted, is associated with rapid and sustained blood count recovery. 16 The benefits of rapid recovery are reduced hospitalization, blood product usage, and infections. 12,17 The minimum threshold for autologous transplantation is currently defined as 2 ϫ 10 6 CD34 ϩ cells/kg body weight (BW). 18 Many centers use a minimum of 3 ϫ 10 6 CD34 ϩ cells/kg BW for myeloablative and nonmyeloablative allogeneic and matched unrelated transplantations. Furthermore, Ͼ 5 ϫ 10 6 CD3...

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“…PB was collected by retroperitoneal puncture 2 h after administration of the last dose of drug (42).…”

Section: Mobilization Of Peripheral Blood (Pb) Hematopoietic Progenitmentioning

confidence: 99%

R-Ras and Rac GTPase Cross-talk Regulates Hematopoietic Progenitor Cell Migration, Homing, and Mobilization

Shang

Cancelas

et al. 2011

Journal of Biological Chemistry

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Pharmacological inhibition of EGFR signaling enhances G-CSF–induced hematopoietic stem cell mobilization

Cited by 60 publications

References 40 publications

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

How I treat patients who mobilize hematopoietic stem cells poorly

R-Ras and Rac GTPase Cross-talk Regulates Hematopoietic Progenitor Cell Migration, Homing, and Mobilization

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