Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “leukemia stem cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1979

Expression of Fv-4r allele in hematopoietic cells from G mice resistant to Friend leukemia virus.

G mice carrying the Fv-4r resistant allele supported virus growth neither at an early nor a later (Kai et al., 1976) stage of infection with NB-tropic FLV. This resistance could not be abolished by treatment of G mice with cyclophosphamide or cortisone acetate. By bone-marrow or spleen-cell transplantation into irradiated mice, the resistan-e of G mice could be transferred to Fv-4-susceptible mice. Conversely, transfer of bone-marrow or spleen cells of Fv-4-susceptible mice rendered G mice susceptible. It could be concluded that, as assessed by the virus content in the spleen, helper LLV grows mainly in radiosensitive, bone-marrow-derived cells, and the Fv-4 gene is expressed in these cells.

Alleles↗
PubMed1979

Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.

A latent form of persistent infection can be established in susceptible adult mice inoculated with a preparation of defective Friend spleen focus-forming virus (SFFV) purified free from standard leukemia-inducing helper virus (LLV-F). SFFV persistence was initially observed using an in vivo rescue technique in which SFFV could be directly rescued to form splenic foci of malignant erythropoiesis in mice. At approximately 30 d after virus inoculation however, SFFV could not be rescued after inoculation of LLV-F indicating that persistently infected (i.e., SFFV+) mice were either immume to exogenous helper virus or able to express SFFV-associated defective-interfering (DI) function(s). Persistent infection by SFFV was further documented using an in vitro rescue technique and ultimately resulted in the induction by SFFV of erythroleukemia in the absence of polycythemia or overt virus production. However, SFFV rescued by LLV-F from persistently infected normal and transformed hemopoietic cells was able to induce polycythemia in adult mice suggesting that this is a helper controlled property of the Friend virus complex. Transplantable SFFV-induced erythroleukemic cells could be retrieved from persistently infected yet histologically normal mice. The duration of SFFV persistence in normal spleen tissue suggests that the SFFV provirus resides in either a long-lived or pluripotent hemopoietic cell. Further, certain changes occurred, presumably in the membranes of persistently infected cells, which preceded the overt development of Friend leukemia and facilitated the definition of an SFFV preleukemic phase. Cell surface alterations were revealed using cell transfer techniques. Hemopoietic cells harboring a rescuable SFFV failed to proliferate when inoculated into lethally irradiated, syngeneic adult mice. In contrast, the transformed progeny of preleukemic cell populations and spleen cells transformed by FV complex (i.e., cells replicating both SFFV and LLV-F) were not rejected. This result suggests that histologically normal SFFV+ preleukemic cells express an antigen recognition site which is not present on overtly transformed cells and which may be a pertinent surveillance target for host anti-leukemogenic reactions.

Animals↗
PubMed1977

Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage.

Glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes types of granulocytes were determined in eight women with chronic myelocytic leukemia (CML). The patients were heterozygous at the X-linked G-6-PD locus for the common gene, GdB, and a variant, such as GdA, so that both B and A enzyme types were found in skin cells. In contrast to these normal cells, only one G-6-PD type was found in CML granulocytes. The fact that such single-enzyme phenotypes are found in CML granulocytes, but not in nonleukemic granulocytes, provides strong evidence that the disease has a clonal origin. Single-enzyme phenotypes were also found in erythrocytes, platelets and cultured blood macrophages indicating that these cells have a common stem cell which is the site of the abnormality in CML. In the one studied patient, no evidence was found for involvement of cultured marrow fibroblasts. Clonal origin of CML virtually excludes cell recruitment as a sole pathogenetic mechanism. Either the leukemia arises as a consequence of a rare initial event in a single cell, or a series of events occurs in a clone such that it evolves into CML, or both.

Adolescent↗
PubMed1977

Mammary tumor and leukemia in male Sprague-Dawley rats evoked by a series of intragastric administration of 7,12-dimethylbenz(a)anthracene.

A series of administration of 7,12-dimethylbenz[a]anthracene given at biweekly intervals by gastric intubation of juvenile male rats of the Sprague-Dawley strain elicited considerable number of mammary carcinomas, leukemias, and ear duct tumors. The evoked leukemia shared two main types; 51.6% of erythroblastic stem cell and 48.4% of myelogenous.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Physiopathology of human and virus-induced murine leukemias.

The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoietic proliferation and maturation is accompanied by a marked cell loss and provokes enlargement of the stem cell compartment. The so-called leukemic cells have a limited proliferation capacity and may not be truly malignant as opposed to blastic cells in acute leukemias. Clinical, hematological, and physiopathological data that are presently available in chronic granulocytic leukemia, polycythemia vera, and the erythroblastic component of erythroleukemia are compatible with the Friend physiopathological model. It is suggested that these differentiated leukemias initiate from an uncontrolled differentiation of a committed cell compartment, which stimulates proliferation of the stem cell compartment. The disease would be due to a proliferation and accumulation of "subnormal" cells characterized by a shorter mean life-span than the normal differentiated cell population. Although limited, the data available suggest that the physiopathology of acute leukemias is clearly distinguishable from that of differentiated leukemias; several immunological and therapeutic applications of this model are outlined.

Animals↗
PubMed1978

Cellular distribution of hemoglobin F in a clonal hemopoietic stem-cell disorder.

Because all erythroid cells in chronic myelogenous leukemia are believed to arise from a common pluripotent stem cell, we studied the cellular distribution of fetal hemoglobin in patients with the disease to test whether cells with and without hemoglobin F have a common or separate pluripotent stem-cell origin. In a patient with chronic myelogenous leukemia and sickle/beta thalassemia, 17 per cent of the red cells during remission and 18 to 22 per cent during the blastic phase contained fetal hemoglobin. In 24 non-hemoglobinopathic leukemic patients 0.3 to 28 per cent of red cells contained hemoglobin F. Since the erythrocytes in chronic myelogenous leukemia are almost exclusively derived from the malignant clone, these data suggest that cells containing fetal hemoglobin originate from the same pluripotent stem-cell progenitor as those without hemoglobin F. The findings argue against a separate line of "partially switched" pluripotent stem cells as being responsible for maintenance of hemoglobin F production in the adult.

Adult↗
PubMed2026

[Development of universal off-the-shelf T cell therapies derived from ES/iPS cells for leukemia and COVID-19].

Cancer immunotherapy using patient-derived T cells genetically modified in vitro has been demonstrated to be effective. However, issues such as cost, time, and unstable quality must be resolved. To overcome these barriers, we developed the TCR-PS cell method, in which a specific TCR gene is introduced into pluripotent stem cells (PS cells), such as ES cells or iPS cells, and T cells are generated from those PS cells. We are currently preparing for a clinical trial in acute myeloid leukemia, targeting the WT1 antigen, with iPS cells provided by the CiRA Foundation as the starting material. In parallel, we are also investigating this approach for viral infections and preparing for clinical trials in COVID-19, with HLA-deficient ES cells as the starting material. This method should enable stockpiling of T cell therapies against known viruses such as SARS or avian influenza. Even for outbreaks caused by unknown viruses, it should be possible to produce T cell therapies within 100 days after the virus genome is defined.

Humans↗
PubMed1979

Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.

Adult↗
PubMed2026

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45 + leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans↗
PubMed2026

Deficiency of Setd2 in mesenchymal stem cells facilitates the progression of myelodysplastic syndrome to leukemia.

While previous studies have indicated that H3K36me3, which is mediated by Setd2, may regulate the cell fate of mesenchymal stem cells (MSCs) both in vitro and in vivo, the specific role of MSCs in the onset and progression of MDS remains unclear. Thus, the histone methyltransferase Setd2 is implicated in MDS-associated leukemia. This study utilized NUP98-HOXD13 (NHD13) mice with targeted deletion of Setd2 in MSCs. Here, we found that Setd2-deficient mice undergo faster leukemia transformation than control mice do, as evidenced by the abnormal differentiation of hematopoietic stem progenitor cells in the bone marrow, abnormal hematopoiesis, and increased number of blast cells. Compared with that of control mice, the morphology of NHD13 mouse MSCs with Setd2 deficiency was irregular, and the support function of hematopoietic cells was compromised. This study demonstrated that targeted deletion of Setd2 in MSCs facilitates the advancement of MDS. Furthermore, we identified increased expression of coagulation factor XII as a key leukemic transformation mediator in Setd2-deficient MSCs. Moreover, we found that SETD2 expression is significantly lower in high-risk MDS patients than in low-risk MDS patients, further suggesting that the targeted deletion of Setd2 in MSCs is associated with MDS progression. Collectively, our results suggest that Setd2 in MSCs suppresses MDS progression to leukemia through coagulation factor XII-mediated suppression of the stem cell support capacity of MSCs. Overall, this study sheds light on the pathogenesis of MDS and provides a therapeutic strategy for regulating the microenvironment in patients with MDS who cannot be cured by haematopoietic stem cell transplantation.

Animals↗