Absence αof 4 Integrin in Hemopoietic Stem Cells Limits Their Self-Renewal Potential in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 118-118
Author(s):  
Thalia Papayannopoulou ◽  
Gregory V. Priestley ◽  
Linda M. Scott
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Self Renewal ◽  
Post Transplant ◽  
Adult Mice ◽  
Cell Niche

Abstract We have previously shown that bone marrow (BM) cells from adult mice with conditional ablation of α4 integrin transplanted into lethally-irradiated recipients have a partial impairment in their homing and especially their short-term engraftment (MCB, 23:9349, 2003). However, the ability of α4−/− stem cells (HSC) to maintain post-transplant long-term hematopoiesis and to self renew was not tested. Therefore, we performed competitive repopulation experiments: α4+/+ cells mixed in equal proportions with α4−/− cells (verified by FACS) were given to each of 10 lethally irradiated recipients (0.5x10 6/mouse). At 30, 100, 200, and 298 days post-transplant, engraftment was evaluated in blood (PB) and BM. By d. 200, 7 of the 9 surviving mice had 81.6±3% α4+/+ cells in their PB and 97.5±0.1% in their BM. In the remaining 2 mice the proportion of α4+/+ PB cells was 35.6±12%, however by d. 298 increased (93.4±2.5% in BM). To overcome a putative partial homing defect for long-term repopulating cells, similar to the one documented using a surrogate CFU-C assay, we repeated the competitive repopulation experiment using not only 1:1, but an increased ratio of α4−/− cells to 3:1 (or 6:1 by CFU-C ratio) given in splenectomized recipients. By 12 wks α4+/+ cells among Gr1+ were 77±3.7% in PB in 10 mice with 1:1 initial transplant and 79±3.8% in 10 given 3:1 cells. These results showed that 4+/+ cells greatly outcompete the α4−/−cells and contributions by α4−/− cells are lost early and late post-transplant. Further insight was provided by transplantation of α4−/− HSC without competitor cells. 12 mice transplanted with α4−/− BM cells were sacrificed at 2 wks (6 mice), at 10 wks (3 mice) and 1 year (3 mice) later. Despite normal PB counts, evaluation of bone marrow and spleen at all times post-transplant showed subnormal values for progenitor cells vs. concurrently transplanted controls. 10 wks post-transplant 1 of the 3 mice sacrificed showed ~50% α4+/+ cells in circulation, while the other 2 had mostly α4−/− cells. From the latter (pooled BM), 2° transplants were carried out and sacrificed 14 wks later. At that time the 5 recipients had 27.5%±4.7 α4+/+ cells in their circulation. At 1 year the 3 primary transplant surviving mice had mostly α4−/− hematapoiesis and served as donors (pooled BM) for 2° transplants (n=9), evaluated 26 wks later. 5 of 9 2° recipients showed mostly α4+/+ cells, whereas 4 recipients had a mean of 6.8±1.9% α4+/+ cells in their blood. Each of these 4 recipients served as a 3° donor for 20 transplants (5/donor) which again were evaluated 25 wks later. There was a 30% survival at that time, and all 6 surviving mice were reconstituted with α4+/+ cells (multi-lineage; contributed by host and not by non-ablated donor stem cells). These data suggested that although long-term repopulation can be established with α4−/− cells in 1°recipients, hematopoiesis is quantitatively abnormal and cannot be sustained beyond a 2° transplant. Taken together, all our transplantation experiments provide compelling evidence that α4−/− HSC have a competitive disadvantage compared to +/+ cells in transplantation, and a deficit in maintaining normal hematopoiesis and stem cell self-renewal. We speculate that α4−/− HSC either are not settled to extramedullary niches supporting sustained hematopoiesis, or do not respond to signals emanating from the stem cell niche. Either way, the data underscore the requirement of α4 integrin in the interaction of HSC with the stem cell niche in order to realize their full self-renewal potential.

Ectopic Human Mesenchymal Stem Cell-Coated Scaffolds Create An In Vivo Leukemia Niche in NOD/SCID Mice.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 559-559
Author(s):  
Sarah Rivkah Vaiselbuh ◽  
Morris Edelman ◽  
Jeffrey Michael Lipton ◽  
Johnson M. Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Scid Mice ◽  
Cxcr4 Antagonist ◽  
Cell Niche

Abstract Abstract 559 Introduction: Different cellular components of the normal hematopoietic niche have been identified. However, the niche for malignant hematopoiesis remains to be elucidated. Recent work of other groups has suggested that hematopoietic stem cells (HSC) within the bone marrow anchor themselves in place by attaching to osteoblasts and/or vascular sinusoid endothelial cells. We have recently identified mesenchymal stem cells (MSC) as niche-maker cells and found a crucial role of the SDF-1/CXCR4 axis in this process. Stromal Derived Factor-1 (SDF-1/CXCL12) regulates stem cell trafficking and the cell cycle via its receptor CXCR4. Methods: Polyurethane scaffolds, coated in vitro with human bone marrow MSC, were implanted subcutaneously in non-irradiated NOD/SCID mice. CD34+ HSC or primary AML cells (from a leukapheresis product) were injected either in situ or retro-orbitally in the mice and analyzed for engraftment. The mice were treated twice per week with in situ injections of SDF-1, AMD3100 (a CXCR4 antagonist) or PBS (control). After 2 to 4 weeks, the scaffolds were processed and evaluated for cell survival in the mesenchymal niche by immunohistochemistry. Results: We created in vitro MSC-coated scaffolds that retained inoculated AML cells in the presence of SDF-1, while AML cells seeded on empty scaffolds were not retained. In vivo in NOD/SCID mice, the MSC-coated scaffolds, in the presence of SDF-1 enabled homing of both in situ injected normal CD34+ HSC and retroorbital- or in situ injected primary human AML cells. The scaffolds were vascularized and showed osteoclasts and adipocytes present, suggestive of an ectopic human bone marrow microenvironment in the murine host. Finally, the SDF-1-treated scaffolds showed proliferation of the MSC stromal layer with multiple adherent AML cells, while in the AMD3100-treated scaffolds the stromal lining was thin and disrupted at several points, leaving AML cells free floating in proximity. The PBS-treated control-scaffold showed a thin single cell MSC stromal layer without disruption, with few AML cells attached. Conclusion: The preliminary data of this functional ectopic human microenvironment in NOD/SCID mice suggest that AMD3100 (a CXCR4 antagonist) can disrupt the stem cell niche by modulation of the mesenchymal stromal. Further studies are needed to define the role of mesenchymal stem cells in maintaining the hematopoietic/leukemic stem cell niche in vivo. In Vivo Leukemia Stem Cell Niche: (A) Empty polyurethane scaffold. (B)Vascularization in SQ implanted MSC-coated scaffold (s) niche in NOD/SCID mice. (C) DAB Peroxidase (brown) human CD45 positive nests of AML cells (arrows) 1 week after direct in situ AML injection. (D) Human CD45 positive myeloid cells adhere to MSC in vivo (arrows). Disclosures: No relevant conflicts of interest to declare.

Cellular and molecular basis of haematopoiesis

2020 ◽  
pp. 5172-5181
Author(s):  
Paresh Vyas ◽  
N. Asger Jakobsen
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Number ◽  
Stages Of Development ◽  
Self Renewal ◽  
Haematopoietic System

Haematopoiesis involves a regulated set of developmental stages from haematopoietic stem cells (HSCs) that produce haematopoietic progenitor cells that then differentiate into more mature haematopoietic lineages, which provide all the key functions of the haematopoietic system. Definitive HSCs first develop within the embryo in specialized regions of the dorsal aorta and umbilical arteries and then seed the fetal liver and bone marrow. At the single-cell level, HSCs have the ability to reconstitute and maintain a functional haematopoietic system over extended periods of time in vivo. They (1) have a self-renewing capacity during the life of an organism, or even after transplantation; (2) are multipotent, with the ability to make all types of blood cells; and (3) are relatively quiescent, with the ability to serve as a deep reserve of cells to replenish short-lived, rapidly proliferation progenitors. Haematopoietic progenitor cells are unable to maintain long-term haematopoiesis in vivo due to limited or absent self-renewal. Rapid proliferation and cytokine responsiveness enables increased blood cell production under conditions of stress. Lineage commitment means limited cell type production. The haematopoietic stem cell niche is an anatomically and functionally defined regulatory environment for stem cells modulates self-renewal, differentiation, and proliferative activity of stem cells, thereby regulating stem cell number. Haematopoietic reconstitution during bone marrow transplantation is mediated by a succession of cells at various stages of development. More mature cells contribute to repopulation immediately following transplantation. With time, cells at progressively earlier stages of development are involved, with the final stable repopulation being provided by long-lived, multipotent HSCs. Long-term haematopoiesis is sustained by a relatively small number of HSCs.

scholarly journals Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo

Blood ◽  
1996 ◽  
Vol 88 (8) ◽  
pp. 2852-2858 ◽  
Author(s):  
R Pawliuk ◽  
C Eaves ◽  
RK Humphries
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Fetal Liver ◽  
Complete Recovery ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Adult Mice

Recent assessment of the long-term repopulating activity of defined subsets of hematopoietic cells has offered new insights into the characteristics of the transplantable stem cells of this system; however, as yet, there is very little known about mechanisms that regulate their self-renewal in vivo. We have now exploited the ability to quantitate these cells using the competitive repopulating unit (CRU) assay to identify the role of both intrinsic (ontological) and extrinsic (transplanted dose-related) variables that may contribute to the regulation of CRU recovery in vivo. Ly5.1 donor cells derived from day-14.5 fetal liver (FL) or the bone marrow (BM) of adult mice injected 4 days previously with 5-fluorouracil were transplanted at doses estimated to contain 10, 100, or 1,000 long-term CRU into irradiated congenic Ly5.2 adult recipient mice. Eight to 12 months after transplantation, there was a complete recovery of BM cellularity and in vitro clonogenic progenitor numbers and a nearly full recovery of day-12 colony-forming unit-spleen numbers irrespective of the number or origin of cells initially transplanted. In contrast, regeneration of Ly5.1+ donor-derived CRU was incomplete in all cases and was dependent on both the origin and dose of the transplant, with FL being markedly superior to that of adult BM. As a result, the final recovery of the adult marrow CRU compartment ranged from 15% to 62% and from 1% to 18% of the normal value in recipients of FL and adult BM transplantation, respectively, with an accompanying maximum CRU amplification of 150-fold for recipients of FL cells and 15-fold for recipients of adult BM cells. Interestingly, the extent of CRU expansion from either source was inversely related to the number of CRU transplanted. These data suggest that recovery of mature blood cell production in vivo may activate negative feedback regulatory mechanisms to prematurely limit stem cell self-renewal ability. Proviral integration analysis of mice receiving retrovirally transduced BM cells confirmed regeneration of totipotent lymphomyeloid repopulating cells and provided evidence for a greater than 300-fold clonal amplification of a single transduced stem cell. These results highlight the differential regenerative capacities of CRU from fetal and adult sources that likely reflect intrinsic, genetically defined determinants of CRU expansion but whose contribution to the magnitude of stem cell amplification ultimately obtained in vivo is also strongly influenced by the initial number of CRU transplanted. Such findings set the stage for attempts to enhance CRU regeneration by administration of agents that may enable full expression of regenerative potential or through the expression of intracellular gene products that may alter intrinsic regenerative capacity.

The Tyrosine Kinase c-Met Is Selectively Expressed on Motile Hematopoietic Progenitors Following G-CSF Administration and Promotes Mobilization by Regulating Stem Cell Niche Components.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3376-3376
Author(s):  
Melania Tesio ◽  
Alexander Kalinkovich ◽  
Amir Schajnovitz ◽  
Ayelet Dar ◽  
Orit Kollet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Beta Catenin ◽  
Hematopoietic Progenitor ◽  
Dynamic Changes ◽  
Kinase C ◽  
Cell Niche

Abstract Application of stress signals such as chemotherapy or repetitive cytokine stimulations induces proliferation, differentiation and mobilization of stem cells from their bone marrow (BM) niches to the circulation, as part of host defense and repair. G-CSF is currently the preferred mobilizing agent used in the clinical setting. We report here that the tyrosine kinase c-Met, is functionally involved in hematopoietic progenitor mobilization by G-CSF administration. Interestingly, c-Met expression was restricted to motile murine and human hematopoietic progenitor cells. While on mouse BM leukocytes c-Met expression was barely detectable during homeostasis, very high levels were documented following G-CSF. Similarly, in the BM of chimeric NOD/SCID mice previously engrafted with human cells, c-Met expression was almost absent on immature human CD34+ and maturing human CD45+ cells from control untreated mice but significant levels of the receptor were detected following G-CSF delivery on both cell populations. This selective expression was associated with increased transcriptional levels of the main regulator of c-Met transcription, hypoxia inducible factor-1 alpha, (HIF-1alpha). More importantly, blockage of c-Met signaling in Balb/c or C57/Bl mice reduced G-CSF-induced mobilization: co-injection of neutralizing c-Met antibodies decreased progenitor cell proliferation in the BM and the release to the peripheral circulation of maturing leukocytes, immature progenitors and primitive Sca+/c-kit+/lin− cells. Moreover, c-Met neutralization was also accompanied by reduced secretion of the mobilizing protease MMP-9. Chemotaxis to SDF-1 was also affected by c-Met inhibition. In vivo c-Met blockage decreased migration of murine bone marrow cells to a gradient of SDF-1 in vitro, suggesting a role for c-Met in directional migration. Stem cells anchored to their BM niches are mostly non cycling/non motile, however following G-CSF, the niche undergoes dynamic changes which are essential for stem cell proliferation and egress. Of note, neutralizing c-Met during G-CSF mobilization lead to significant changes of key regulatory components of the stem cell niche. While beta catenin was significantly up-regulated following G-CSF treatment, neutralization of c-Met decreased beta catenin expression on BM hematopoietic cells to levels similar to those observed in control untreated mice. The stem cell anchoring molecule angiopoietin-1 and its receptor Tie-2 were also affected following in vivo c-Met inhibition. BM cells obtain from G-CSF treated mice presented low transcriptional levels of these molecules, whereas c-Met neutralization reduced this inhibitory effect exerted by G-CSF. In conclusion, our data identify c-Met as a new player involved in the regulation of several aspects that characterize G-CSF induced mobilization: proliferation and migration of progenitor cells as well as dynamic changes in the stem cell niche which are required for stress induced proliferation and recruitment of stem cells.

scholarly journals Hemmule: A Novel Structure with the Properties of the Stem Cell Niche

2020 ◽  
Vol 21 (2) ◽  
pp. 539
Author(s):  
Vitaly Vodyanoy ◽  
Oleg Pustovyy ◽  
Ludmila Globa ◽  
Randy J. Kulesza ◽  
Iryna Sorokulova
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Stem ◽  
Novel Structure ◽  
Hematopoietic Stem Cell Niches ◽  
Cell Niche ◽  
Stem Cell Niches ◽  
Rat Bone

Stem cells are nurtured and regulated by a specialized microenvironment known as stem cell niche. While the functions of the niches are well defined, their structure and location remain unclear. We have identified, in rat bone marrow, the seat of hematopoietic stem cells—extensively vascularized node-like compartments that fit the requirements for stem cell niche and that we called hemmules. Hemmules are round or oval structures of about one millimeter in diameter that are surrounded by a fine capsule, have afferent and efferent vessels, are filled with the extracellular matrix and mesenchymal, hematopoietic, endothelial stem cells, and contain cells of the megakaryocyte family, which are known for homeostatic quiescence and contribution to the bone marrow environment. We propose that hemmules are the long sought hematopoietic stem cell niches and that they are prototypical of stem cell niches in other organs.

scholarly journals Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2678-2688 ◽  
Author(s):  
Marisa Bowers ◽  
Bin Zhang ◽  
Yinwei Ho ◽  
Puneet Agarwal ◽  
Ching-Cheng Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem Cell ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Leukemia Development

Key Points Bone marrow OB ablation leads to reduced quiescence, long-term engraftment, and self-renewal capacity of hematopoietic stem cells. Significantly accelerated leukemia development and reduced survival are seen in transgenic BCR-ABL mice following OB ablation.

Autologous Stem Cell Transplantation (ABMT) for Recurrent Hodgkin’s Disease from 1990–2005: Factors Contributing to Post-Transplant Relapse.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2083-2083
Author(s):  
Brian Bolwell ◽  
Brad Pohlman ◽  
Matt Kalaycio ◽  
Steve Andresen ◽  
Elizabeth Kuczkowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Prior Chemotherapy ◽  
Post Transplant ◽  
Peripheral Stem Cells

Abstract Long-term results of conventional therapy of Hodgkin’s disease (HD) has demonstrated the importance of long-term and ongoing follow-up given the potential for later complications after curative therapy. While many transplant series report follow-up of several years after ABMT, few report a 15-year experience from a single institution. This report examines the outcomes of 220 patients receiving high-dose chemotherapy and autologous stem cell transplant (ABMT) at The Cleveland Clinic Foundation from January 1990 through June 2005. Median age was 33 years (range, 14–70 years); median time from diagnosis to transplant was 19 months; 47% received prior radiation therapy; 82% had nodular sclerosis histologic subtype; number of courses of prior chemotherapy were: 1 (16%), 2 (66%), 3 (14%), 4 or more (4%). All patients received salvage therapy prior to transplant: 29% were in a complete remission (CR), 55% in a partial remission (PR), and 16% refractory. All patients received a chemotherapy-only preparative regimen, most commonly Bu/Cy/VP (73%), followed by CBV (17%). 78% received peripheral stem cells alone; 22% received either autologous bone marrow or a combination of bone marrow plus peripheral stem cells. At the present time 60% of patients are alive. Of the 88 patients who died, the most common cause of death is relapse (69% of deaths). Secondary malignancy occurred in 11 patients (5%); 9 of these cases were secondary AML/MDS and 5 of these patients with secondary malignancies have died. 44% of the entire cohort has relapsed, at a median of 9 months post-transplant (range, 1.4–76 months). 10-year overall survival is 47%. A multivariable analysis showed that the two significant variables that correlated with post-BMT relapse were the number of prior chemotherapies (p = 0.011), and patients treated in remission vs. those not in remission (p = 0.002). Of patients receiving 2 or more prior courses of chemotherapy, 60% have relapsed 8 years post-transplant, compared to 40% of those receiving one course of prior chemotherapy. The risk of relapse by the number of prior chemotherapy courses is shown graphically below: Figure Figure In conclusion, this very large series of ABMT for recurrent HD with long-term follow-up demonstrates the importance of timely autografting in relapsed HD patients. The optimal time to proceed with ABMT is after failing one, and only one, course of chemotherapy. Delaying transplant for unrealistic long-term salvage with other courses of traditional chemotherapy will negatively affect the outcome of subsequent ABMT.

Loss of P-Selectin Promotes the Function of Aged Hematopoietic and Leukemic Stem Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1577-1577
Author(s):  
Yaoyu Chen ◽  
Sullivan Con ◽  
Yiguo Hu ◽  
Linghong Kong ◽  
Cong Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Bone Marrow Cells ◽  
Leukemic Stem Cells ◽  
Wild Type ◽  
Post Transplant ◽  
Marrow Cells

Abstract Abstract 1577 Hematopoiesis is a tightly regulated biological process that relies upon complicated interactions between the blood cells and their microenvironment. Adhesion molecules like P-selectin are essential to hematopoiesis, and their dysregulation has been implicated in leukemogenesis. We have previously shown a role for P-selectin in chronic myeloid leukemia and demonstrated that in its absence the disease process accelerates. Recently, there has also been speculation that P-selectin may play a role in the aging hematopoietic stem cells (HSCs), as its expression in upregulated as a mouse ages. In this study, we show that the loss of P-selectin function dysregulates the balance of stem cells and progenitors and that these differences become more pronounced with age. We compared the percentages of HSCs, long-term (LT)-HSCs, short-term (ST)-HSCs, multipotent progenitors (MPPs), CMPs, GMPs and MEPs in bone marrow by flow cytometry between wild type (WT) and Selp-/- mice. An age-dependent LT-HSC expansion was observed in WT mice. However, this expansion was prevented by the loss of Selp as observed in Selp-/-mice. Further, we demonstrate that with age LT-HSCs in particular express more elevated levels of P-selectin. LT-HSCs and ST-HSC/MPPs were isolated from the bone marrow of young (2 months old) and old (15 months old) WT mice and examined P-selectin expression by FACS. A significant increase in P-selectin expression was observed in LT-HSCs of old mice, and this increase was not observed in the ST-HSC+MPP subpopulations. We also show that the loss of P-selectin gene has profound effects of stem cell function, altering the capacity of these cells to home. Despite impaired homing capacity, stem cells lacking P-selectin possess a competitive advantage over their wild type counterparts. Using a stem cell competition assay, HSCs derived from Selp-/- mice (CD45.2+) and WT control mice (CD45.2+GFP+) were mixed in 1:1 ratio and transplanted into irradiated WT recipients (CD45.1). The initial findings were potentially indicative of the ability of cells derived from GFP mice to more efficiently home and engraft. Despite this initial advantage, cells derived from Selp-/- eventually exhibited a competitive and statistically significant advantage over the cells derived from GFP mice. At 30 days post-transplant, 49.9±1.4% of the CD45.2 subpopulation was GFP+. At 86 days post-transplant, 25.7±3.3 % of the CD45.2 cells derived from the peripheral blood were GFP+. Similarly, 23.0±3.7% of the CD45.2 cells derived from the bone marrow of these mice were GFP+. Indeed, we demonstrate that recipients of P-selectin deficient bone marrow cells more efficiently repopulate the bone marrow than controls and that this advantage extends and expands in the long-term. Finally, we demonstrate that recipients of leukemic cells lacking P-selectin develop a more accelerated form of leukemia accompanied by significant increases in stem and progenitor cells. Bone marrow cells from donor WT and Selp-/- mice were infected with retrovirus expressing BCR-ABL-GFP, and irradiated WT recipients were transplanted with 2×105 of these transduced donor cells. At 14 days post-transplant, recipient mice from each of the groups were sacrificed, and bone marrow cells were harvested and analyzed by flow cytometry. Recipients of leukemic Selp-/- cells possessed 3.5-fold more LSCs than recipients of wild-type cells. There were 3.1-fold more LT-LSCs and 3.8-fold more ST-LSCs and MPPs in recipients of Selp-/- cells than WT cells. In addition, recipients of leukemic Selp-/- cells possessed significantly more CMP (16.9-fold) and MEP (4.5-fold) cells. Because P-selectin expression increases with age on LT-HSCs, we sought to determine the role that age plays in CML development and progression. Bone marrow cells derived from 15-month-old donor Selp-/- and WT mice were transduced with BCR-ABL, respectively, followed by transplantation of the transduced cells into recipient mice. All recipients of BCR-ABL transduced Selp-/- cells died by 23 days after induction of CML and had a median survival of 19 days, whereas recipients of the transduced WT cells survived significantly longer. This pro-leukemic role for cells lacking P-selectin expression is leukemic stem cell-specific rather than stromal cell-specific and supports an essential role for P-selectin on leukemic stem cells. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document