Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is a lethal malignancy of the human hematopoietic stem cell. Here we report that coexistent benign, primitive hematopoietic progenitors can be distinguished from their malignant counterparts in CML bone marrow by differences in cell surface antigen expression. Selection of bone marrow cells expressing the CD34 antigen but lacking the HLA-DR antigen results in recovery of small lymphocyte-like blasts, which initiate and sustain production of myeloid clonogenic progeny in vitro. Secondary clonogenic cells derived at week 1, 5, and 8 from long-term bone marrow cultures (LTBMCs) initiated with primitive progenitors, which lack HLA-DR antigens, exhibit neither the Philadelphia chromosome (Ph1) nor the corresponding bcr/abl mRNA characteristic of CML. In contrast, clonogenic cells recovered at week 1, 5, and 8 from LTBMCs initiated with the CML HLA-DR+ population contain Ph1 and express bcr/abl mRNA. This observation indicates that it may be possible to select a population of viable, exclusively benign hematopoietic stem cells from CML bone marrow capable of repopulating the hematopoietic compartment following autologous bone marrow transplantation.
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PMID:Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression. 137 Oct 77

Our previous studies have shown that a unique glycoprotease from Pasteurella haemolytica specifically cleaves only proteins containing sialylated O-linked glycans. The hematopoietic progenitor cell antigen, CD34, which is heavily glycosylated with both N- and O-linked glycans, is readily cleaved by this protease. In this study, we demonstrate that the epitopes detected by five of the seven CD34 monoclonal antibodies are removed by the glycoprotease. The differential sensitivity of the CD34 epitopes to cleavage with either neuraminidase and/or glycoprotease establishes three classes of epitopes: 1) (class I) those identified by MY10, B1.3C5, 12.8, and ICH3 that are differentially affected by neuraminidase and removed by the glycoprotease; 2) (class II) the epitope detected by QBEND 10 that is removed only by the glycoprotease; and 3) (class III) those identified by TUK3 and 115.2 that are not removed by either enzyme. Cleavage of the 110-kd CD34 structure by the glycoprotease generates a major cell-bound fragment of about 75 kd, identified by the class III antibodies. We have also used the enzyme to improve the rapid recovery of CD34+ cells selected by immunomagnetic affinity techniques. In a preclinical model, we separated CD34+ KG1 cells with high yield (90%-95%) and high purity (94%-98%) from sham mixtures containing 50% CD34- cells. We also separated CD34+ blast cells from a patient in megakaryoblastic crisis of chronic myelogenous leukemia. In this case, the purity and yield were 93% and 94%, respectively. Enzyme treatment had no detrimental effect on cell viability, and the treated cells showed a normal quantitative expression and distribution of CD34 antigen as assessed with class III antibodies. We conclude that the P. haemolytica glycoprotease has potential to improve the isolation, from human bone marrow, of primitive hematopoietic cells that carry the CD34 antigen.
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PMID:Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica glycoprotease: implications for purification of CD34-positive progenitor cells. 137 60

Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were seen as isolated, randomly distributed mononuclear cells in normal and regenerating bone marrows. Conversely, QBEND10+ cells were increased and present in aggregates of three or more cells in 6/8 cases of acute leukemia; in two cases of CD34-negative leukemia and in two patients after complete remission no aggregates were seen. QBEND10 immunohistochemistry may therefore be useful for diagnosis and follow-up of myeloid leukemias. In addition, increased numbers of CD34+ cells arranged in clusters were seen in 4/9 cases of refractory anemia with excess blasts (RAEB), 1 case of chronic myelomonocytic leukemia, 3/3 cases of RAEB in transformation, and in 3/7 cases of chronic myelogenous leukemia: in all these cases, CD34 staining of the bone biopsy may have prognostic value. QBEND10+ endothelial cells were significantly increased in all the pathological conditions examined (1.43% of all nucleated cells versus 0.80% in normal bone marrow; p = 0.0063), but especially in myeloid leukemias and in two fibrotic syndromes examined.
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PMID:Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody. 172 30

Cells from patients with acute myeloid leukaemia (AML) or chronic myeloid leukaemia (CML) were separated into CD34-enriched and CD34-depleted subpopulations. The clonogenic capacities of these two subpopulations were then compared to each other and to the original unseparated cell population. In every study, the CD34-enriched subpopulation demonstrated a substantial increase in clonogenicity in vitro in comparison with the original cell population, while the reverse was the case for the CD34-depleted subpopulations. For reasons not clear at present, the enrichment for clonogenic cells far exceeded the enrichment for cells expressing the CD34 antigen. Additionally, the clonogenic potential was found to be unrelated to the level of myc expression in the various cell populations.
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PMID:Clonogenic potential of myeloid leukaemia cells in vitro is restricted to leukaemia cells expressing the CD34 antigen. 750 65

The c-kit proto-oncogene is the receptor gene for the stem cell growth factor. Little is known about the distribution and role of this gene product in malignant hematopoiesis. We analysed here the expression of c-kit in myeloproliferative disorders (MPDs), including chronic myelogenous leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF) and in the myelodysplastic syndromes (MDS). The c-kit expression of peripheral blood mononuclear cells was measured both at the messenger RNA level using Northern analysis, the RNA dot blot technique with densitometric quantification, the sensitive reverse transcription polymerase chain reaction, and at the protein level using immunofluorescence with monoclonal antibodies. There was a statistically significant increase in c-kit messenger levels in CML, ET, PV, IMF, and MDS as compared with controls (healthy volunteers). The percentage of c-kit protein expressing cells was also higher than in the controls in these disorders. There was a significant correlation of the c-kit protein expression with the CD34 antigen of the cells. Expression correlated with the phase of the disease, being highest in the blast crisis of CML and in the RAEB/RAEBt phases of MDS. The data suggest that increased amounts of circulating stem/progenitor cells with c-kit receptor are found in MPDs and MDS. It is possible that elevated c-kit expression could maintain the affected clone in MPDs and MDS.
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PMID:Expression of the c-kit proto-oncogene in myeloproliferative disorders and myelodysplastic syndromes. 751 74

Flow cytometry studies have shown that high expression of CD34 antigen in patients with chronic myeloid leukemia (CML) is indicative of accelerated or blastic phases. It has also been suggested that similar information can be obtained by CD34 immunostaining of bone marrow biopsy specimens. To test this hypothesis, the authors studied 59 conventionally fixed, paraffin-embedded bone marrow trephine biopsy specimens, representing the three phases of the disease (stable, accelerated, and blast crisis). Immunohistochemical staining for CD34 was performed using QBEnd10, a monoclonal antibody reactive in routine paraffin-embedded tissue. The differences in CD34 positivity among chronic, accelerated, and blastic phases of CML were highly significant (P = .0001). This study demonstrated that CD34 immunohistochemical staining of bone marrow biopsy specimens represents a reliable method for classifying patients with CML and may provide essential diagnostic and prognostic information when a marrow aspirate is unavailable.
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PMID:CD34 immunostaining of bone marrow biopsy specimens is a reliable way to classify the phases of chronic myeloid leukemia. 751 85

Chronic myeloid leukemia (CML) is a clonal disorder arising from the hematopoietic stem cell, characterized by the Philadelphia chromosome (Ph) and, at the molecular level, by fusion of the BCR (breakpoint cluster region) gene and the c-ABL gene. The hallmark of CML is represented by a marked increase in the number of leukemic progenitors, as well as more mature cells, in the bone marrow (BM) and peripheral blood (PB). Despite expansion of the leukemic clone, normal Ph-negative stem cells have been demonstrated to survive in CML. Early observations of partial, but transient, restoration of Ph-negative hematopoiesis after high-dose chemotherapy have recently been extended by the use of myeloablative regimens followed by autografting with marrow or blood-derived stem cells. Moreover, treatment of early-stage CML patients with the biologic response modifier alpha-interferon (alpha-IFN) has led to the re-emergence of normal progenitor cells. Concurrently, "in-vitro" studies have reported that cultures of CML marrow in the presence of a stromal feeder-layer resulted in depletion of Ph-positive cells and predominance of Ph-negative hematopoietic precursors. Based on the assumption that normal and malignant stem cells may coexist in CML, several studies have recently been directed toward the characterization and "in-vitro" selection of benign progenitors within CML hematopoiesis. The results of those studies demonstrated that normal precursors can be phenotypically and functionally identified in the BM or PB of Ph-positive CML patients. These cells are included in the earliest identifiable hematopoietic cell compartment. Normal cells do not bear cell surface lymphoid or myeloid-lineage antigens, express high levels of the CD34 antigen, and fail to express the HLA-DR antigen. Furthermore, they possess a great capacity for adhering to marrow stroma. This cell population represents only a small minority of hematopoietic progenitors, but it retains many of the properties associated with putative hematopoietic stem cells. Thus, purification of a population of benign hematopoietic precursors that could be used for autologous bone marrow transplantation (ABMT) may be feasible in CML patients.
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PMID:Characterization and selection of benign stem cells in chronic myeloid leukemia. 817 34

We have evaluated an easy and fast immunomagnetic method for positive selection of cells expressing the CD34 antigen from BM, peripheral blood (PB) and apheresis products (AP) of CML patients and healthy adults (HA) in order to further characterize them by immunophenotypic analysis. From an initial frequency of CD34+ cells in the original sample of 1.8 +/- 1.7%, CD34+ cells were rapidly and efficiently enriched up to 91.5 +/- 6.4% by high-gradient magnetic cell sorting (MACS) (yield 53 +/- 21%). A five-dimensional flow cytometric analysis of the immunomagnetic isolated CD34+ cells demonstrated little overlap between CD34+HLA-DRlo and CD34+CD38lo subpopulations in both BM-HA and in BM-CML. Only 16 and 6% of the CD34+HLA-DRlo and CD34+CD38lo cells respectively, showed lack of expression of both Ag (CD34+HLA-DRloCD38lo) in BM-CML samples. Between 60 and 70% of the CD34+ cells expressed the stem cell factor (SCF) receptor (c-KIT, CD117) and there were no differences between BM-HA and BM-CML patients. Moreover, more than 60% of the CD34+HLA-DRlo cells, co-expressed c-KIT. MACS-enriched BM-CD34+ cells showed normal hematopoietic colony formation in vitro in all the sources analyzed with a higher colony-forming efficiency than the unfractionated sample (MNC).
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PMID:Isolation of CD34+ hematopoietic progenitor cells in chronic myeloid leukemia by magnetic activated cell sorting (MACS). 887 25