A bstract : Using an in vivo selection technique, we can isolate individual cells that can repopulate the hematopoietic system of a lethally irradiated murine recipient. These cells rapidly acquire a CD34 phenotype in the animal. Progenitors in our long‐term chimeras are of donor type. We also have evidence that transplantation of limiting numbers (as low as a single cell) that have this long‐term repopulating ability (LTRA) can self‐renew. This is demonstrated by serial transplantation of marrow from engrafted recipients 11 months post transplant into new hosts for four additional months.
Estrogen appears to be a negative regulator of normal hematopoiesis. Chromosome 6q, which contains the estrogen receptor (ER) gene, is frequently altered in human hematopoietic neoplasms. The ER gene, which has growth and metastasis suppressor activity in many different cell types, is inactivated by promoter methylation in some ER-negative breast tumors and 100% of colorectal tumors. We now report that the promoter region of the ER gene is aberrantly methylated in 86% of human hematopoietic tumors, including 8 of 9 pediatric acute lymphocytic leukemia, 17 of 18 adult acute lymphocytic leukemia, 21 of 23 adult acute myelogenous leukemia, 3 of 6 chronic phase chronic myelogenous leukemia, 9 of 9 blast crisis chronic myelogenous leukemia and 5 of 8 lymphomas. This methylation event was also present in all nine leukemia cell lines examined, where it was associated with very low or absent ER expression. In addition, rat and mouse leukemia cell line also exhibited this change, indicating that ER CpG island methylation in leukemias is conserved among species. Our results suggest that ER CpG island methylation could be an important step in the genesis of human hematopoietic neoplasms and might be a useful molecular marker for monitoring the clinical status of these diseases.
Abstract Simultaneous exposure to the lipophilic dye merocyanine 540 (MC 540) and white light inactivates several enveloped viruses. The same treatment appears to have little or no effect on pluripotent hematopoietic stem cells, mature red cells, and mature leukocytes. At least some components of the clotting system are spared, too. The molecular basis of the virucidal effect of MC 540 and light is not yet completely understood. Based on what is known about the interactions of MC 540 with cells and artificial membranes, it seems likely that MC 540 binds to and damages the viral envelope. MC 540‐mediated photosensitization may have implications for the sterilization of bone marrow and blood products, the preparation of vaccines, and selected areas of antiviral therapy.
The purpose of this report is to demonstrate the phenotypic and functional characteristics of a primitive hematopoietic stem cell (HSC). We present evidence that an isolated murine HSC can repopulate the hematopoietic tissues of lethally irradiated recipient animals long term. By limiting dilution, as few as ten isolated stem cells can reconstitute mice for their lifetime. The stem cell which we have isolated does not copurify with colony forming unit-spleen or radioprotect recipients from lethal radiation. The phenotypic characterization of this rare cell, which represents 0.005% of total bone marrow, includes either the absence or very low expression of markers associated with long-term repopulating cells described by other groups. We believe this stem cell represents a very early self-renewing stem cell in the mouse.
