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S Sharkis

Publications and source records attributed to S Sharkis.

4 recordsLinked to original sources
PubMed1999

Functional activity of murine CD34+ and CD34- hematopoietic stem cell populations.

The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols. Recently, CD34- hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34+ murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34+Lin- vs CD34-Lin- cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34+Lin- and CD34-Lin- cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stem cells; however, the number of hematopoietic stem cells in the CD34+Lin- fraction is approximately 100-fold greater than the number in the CD34-Lin- fraction. In competitive repopulation experiments, CD34+ stem cells are better able to engraft the bone marrow than are CD34- cells. CD34+Lin- cells provide both short- and long-term engraftment, but the CD34-Lin- cells are capable of only long-term engraftment. Ex vivo, the CD34+Lin- stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model. In contrast, when CD34-Lin- cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the bone marrow. Thus, the CD34+Lin- and CD34-Lin- cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution.

Animals↗
PubMed1997

Multilineage gene expression precedes commitment in the hemopoietic system.

We have tested the hypothesis that multipotential hemopoietic stem and progenitor cells prime several different lineage-affiliated programs of gene activity prior to unilineage commitment and differentiation. Using single cell RT-PCR we show that erythroid (beta-globin) and myeloid (myeloperoxidase) gene expression programs can be initiated by the same cell prior to exclusive commitment to the erythroid or granulocytic lineages. Furthermore, the multipotential state is characterized by the coexpression of several lineage-affiliated cytokine receptors. These data support a model of hemopoietic lineage specification in which unilineage commitment is prefaced by a "promiscuous" phase of multilineage locus activation.

Animals↗
PubMed1989

Efficacy of ex vivo purging for autologous bone marrow transplantation in the treatment of acute nonlymphoblastic leukemia.

We used an in vitro measure of drug activity to predict the efficacy of ex vivo purging of leukemic cells from autologous bone marrow grafts. We previously found that the myeloid progenitor cell (CFU-GM) content of the marrow grafts after ex vivo purging with 4-hydroperoxycyclophosphamide (4-HC) correlates with time to hematologic recovery after autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. We observed that variable red blood cell concentration of the bone marrow incubation mixture results in differential cytotoxic activity of 4-HC. The CFU-GM content of the graft after the ex vivo treatment is a measure of this 4-HC activity. We analyzed the disease-free survival of 45 patients with acute nonlymphoblastic leukemia undergoing autologous bone marrow transplantation with 4-HC purged grafts. Patients who relapsed after transplantation had 4.2 +/- 1.1% of graft CFU-GM surviving the ex vivo purge, compared with 1.1 +/- 0.4% for patients who achieved a sustained remission (P = .06). Twenty-three patients with a CFU-GM content after 4-HC purging of greater than 1% of the pretreatment value had an actuarial disease-free survival of 12%, compared to 36% for 22 patients with a less than or equal to 1% CFU-GM content after purging (P = .006). Therefore, percent CFU-GM survival as a measure of 4-HC cytotoxicity identified a group of patients with insufficient purging. Although no randomized clinical trials have documented the need for ex vivo purging, our results suggest that effective bone marrow purging is important for the optimal application of autologous transplantation in the treatment of acute nonlymphoblastic leukemia.

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