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)

We describe for the first time a case report documenting a chronic myelogenous leukemia (CML) patient who developed a blast crisis of natural killer (NK) lymphocytes. Many of the blasts exhibited large granular lymphocytic (LGL) morphology. Single parameter immunophenotyping results determined that the granulated as well as the agranulated blast cells were NK lymphocytes (CD45, NKH1, CD2, LEU 17, and CD16 positive; CD3, CD8, and LEU 7 negative). Dual parameter flow cytometric testing also determined that some of the blasts expressed the CD11b and CD11c markers as reported for some types of NK lymphocytes. Approximately 10% of the cells were in the S phase of the cell cycle as determined by a modified Vindelov DNA content analysis test and may theoretically reflect some of those cells expressing CD11b and CD11c. The cells did not express in vitro NK lymphocyte functional activity against a K562 target and therefore similar to other reported cases of presumably immature NK lymphocytic leukemias. The NK lymphocyte blast crisis was successfully treated with vincristine and prednisone. The patient's disease eventually relapsed and transformed to a progenitor stem cell before she died (CD45, 13, CD38, and CD34 positive). The flow cytometric immunophenotyping results contributed significantly as an important adjunct in determining the appropriate diagnosis, helping to select the type of therapy, and monitoring the patient with this unusual type of blast crisis.
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PMID:Natural killer lymphocyte blast crisis of chronic myelogenous leukemia. 281 23

The immunophenotype of peripheral blood blast cells from 14 patients in the chronic phase of chronic myeloid leukemia (CML) was studied using a panel of monoclonal antibodies (McAb) directed against megakaryocytic, granulomonocytic, erythroid and lymphoid antigenic determinants. The blast cells were enriched by a simple bovine serum albumin (BSA) density-cut separation and cooled in liquid nitrogen. The study was done using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique on the thawed blast cells. A consistent pattern of reactivity with McAb was found in all patients, showing that blast cells were heterogeneous. A minor component of the blast cells react with platelet antibodies, most of them being labelled with anti-GPIIb-IIIa McAb. Anti-GPIb and Von Willebrand factor McAb detected 4 times fewer megakaryocytic blast cells, suggesting that these cells are located very early in the differentiation scheme. Two major blast cell compartments were labelled with early myelomonocytic (anti-CD13: MY7) and early erythroid (anti-CD36: FA6-152) McAb. The CD34 (My10) and DR antigens which are expressed by immature blast cells and myeloid progenitors of human bone marrow (BM) were present on more than 50% of the CML blast cells. Thus, the blast cells of chronic phase CML patients, showed the same cellular diversity as the increased progenitor cell compartment observed in this disease, and their differentiation stages seemed to be very closely related.
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PMID:Immunophenotype of blast cells in chronic myeloid leukemia. 319 45

Cell resistance to pharmaceutical agents arises among other causes because of multiple drug resistance induced by P-glycoprotein (P-gp). The analysis of expression of P-gp and differentiation antigens of hemopoietic cells has been made on myeloid cells from 14 patients in CML chronic phase and 25 with CML acceleration and in blast crisis. Surface antigen expression was evaluated at flow cytofluorimetry (FACScan unit). Fluorescent dye rodomin (Rh123) helped examine P-gp functional activity. A close relationship is shown between P-gp expression and CD34 (r = 0.69. p = 0.0004), this giving evidence of these antigens expression on the same cells. In chronic phase P-gp is expressed on a few cells in some patients, its activity being low or absent. The appearance of UIC-2+ cells was unrelated to previous chemotherapy and brought no resistance to treatment. In terminal stage P-gp is expressed in 50% of cases. Functional tests identified the active protein in blast populations with a large number of UIC-2+ cells and in some patients with a small number of cells expressing P-gp. Therefore, comprehensive clinical investigations are needed of multiple drug resistance, though in half of the resistant patients in AML blast crisis P-gp+ cells were not identified suggesting the existence of other mechanisms responsible for resistance to treatment.
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PMID:[The clinical significance of the expression of the multiple-drug resistance protein P-glycoprotein in chronic myeloleukemia]. 748 97

While immunotyping blast cells from 45 patients with CML blast crisis, we detected 5 cases with immunologically primitive blast cells. The immunological phenotype of these cells corresponded to that of primitive stem cells which are characterized by expression of CD34 and HLA-DR antigens in the absence of other immunological markers. We suggest that blast cells from these patients may undergo differentiation similar to that of primitive stem cells that implies the existence of a new immunological variant of CML blast crisis, a primitive variant. Morphologically, blast cells in 3 cases could be classified as myeloid, in 2 cases precise identification was impossible. Cytochemically, this type of cells can be defined as mixed. The patients with CD34+ phenotype do not differ clinically or hematologically from those with CML blast crisis. Blast cells with membrane marker CD34 are likely to arise in any CML phase either as a component of overall leukemic population or predominant, single subclone.
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PMID:[A "primitive" variant of the blast crisis in chronic myeloleukemia]. 748 98

CD34 monoclonal antibodies (McAbs) are widely used to identify and isolate hemopoietic progenitors and to classify acute and chronic leukemias. We assessed the reactivity of 17 CD34 McAbs from the 5th International Workshop on Leukocyte Differentiation Antigens with a variety of cells types: normal bone marrow hemopoietic progenitors, 10 AML, 6 ALL, 11 CML. The reactivity for these McAbs was compared with that of reference CD34 McAbs (Q-Bend 10 and 8G12). For each cell population the % of McAb binding cells, the peak channel and the mean fluorescence intensity (MFI) of the positive cells was evaluated. The peak channel, the MFI and the number of positive cells varied significantly from case to case, depending on the McAb and the type of leukemia. According to the spectrum of reactivity three groups of McAbs were defined; however, 7 McAbs do not belong to any of these subgroups. These groups were not entirely in accordance with McAb classification based on enzyme cleavage that identified three epitopes of the CD34 molecule. Some reagents were found to be more specific for AML, other for ALL, CML or normal CD34+ cells. Normal bone marrow light density cells showed a significantly higher percentage of positive cells for 43A1 and MD34.2 McAbs compared to that documented for the remaining McAbs. AML cells showed the most variable pattern of expression for the CD34 McAbs. In leukemic samples, MESF (molecular equivalents of soluble fluorochrome) values ranged from 18,200 to 322,000 and the number of binding sites per cells was 5,000-81,000.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD34+ leukemic cells assessed by different CD34 monoclonal antibodies. 749 51

Antigenic profiles in AML that have generally accepted prognostic significance, and allow treatment stratification, have not yet been defined. In a previous report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab YB5.B8 was expressed on about one third of AML cases, mainly of the undifferentiated FAB-subtypes and associated with poor prognosis and overall survival. In this study, the moab 17F11 also directed against the c-kit structure stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL samples were c-kit negative. c-kit was not restricted to any particular, undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML-M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also expressed on CD4+ CD34- precursor cells differentiating towards the monocyte lineage. In addition, multi-color labelings revealed an extraordinary heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+ CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive; two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to clinical outcome c-kit expression as single parameter was not predictive for poor response to therapy and short survival as previously suggested.
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PMID:AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression. 750 33

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

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

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.
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PMID:Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML. 751 51

Long-term culture of marrow from patients with chronic myelogenous leukemia (CML) has been reported to favor the outgrowth of bcr/abl- progenitor cells in some patients. We examined the effect of the presence of soluble or transmembrane forms of stem cell factor (SCF) in long-term cultures of CML marrow. CD34-enriched cells from CML patients in advanced chronic phase or accelerated phase were plated on immortalized fetal liver stromal cells from homozygous SCF-deficient SI/SI mice (SI/SI4) with or without the addition of soluble human SCF, SI/SI4 cells expressing high levels of the transmembrane form of human SCF (SI/SIh220), or primary human allogeneic stroma. Cells were removed from cultures and plated weekly in colony assays. The clonagenic cell output from cultures completely lacking SCF was lower over the first 2 to 3 weeks, but by 5 weeks was similar to the clonagenic cell output from the other culture conditions. Analysis of bcr/abl transcripts from individual colonies showed a lower percentage of malignant progenitors present in long-term cultures completely deficient in SCF than under the other culture conditions, particularly compared with primary human stroma-containing long-term cultures. SCF may specifically favor malignant versus benign progenitor cells present in the marrow of CML patients, and an abnormal proliferative response to SCF in very primitive cells may be an underlying defect in the pathophysiology of this disease.
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PMID:Long-term culture of chronic myelogenous leukemia marrow cells on stem cell factor-deficient stroma favors benign progenitors. 753 38


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