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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 characterized by two distinct phases--chronic and acute. Features of the chronic phase include proliferation and accumulation of mature myeloid cells and their progenitors; differentiation is seemingly intact. In contrast, the acute phase is characterized by impaired differentiation. Acute phase is heterogeneous--granulocytes, lymphocytes, megakaryocytes, and erythroid cells are involved singly or in combination. The t(9;22) translocation, which results in the Ph1 chromosome, is the hallmark of chronic phase CML. Transition to acute phase is often accompanied by additional chromosome abnormalities. Here we suggest that these additional abnormalities determine the phenotype of acute phase CML.
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PMID:Do chromosome abnormalities determine the type of acute leukemia that develops in CML? 229 2

To examine the role of DNA methylation in breakpoint location of chromosomal translocation, HpaII sites in and flanking the M-bcr on chromosome 22 were mapped in DNA from blood granulocytes and lymphocytes, bone marrow cells, thymic tissue, and spermatozoa from normal individuals. Allelic HpaII sites were identified clustered in a 600-base pair genomic area of the M-bcr. Bone marrow cells and blood granulocyte DNA showed identical allelic patterns. Thymic tissue and blood lymphocytes showed identical allelic patterns distinct from bone marrow cells and blood granulocytes. Spermatozoa showed a third methylation pattern. In all individuals, the HpaII sites were present within the BamHI/BglII fragment of the M-bcr, the same area associated with high breakpoint frequency in chronic myelogenous leukemia (CML). Three of 15 patients with chronic phase CML showed fully methylated rearranged BglII/BglII M-bcr restriction fragments not seen in normal bone marrow cells. These methylation patterns of the M-bcr may be important in CML breakpoint location and may be a marker for tissue differentiation.
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PMID:Presence of cell lineage-specific hypomethylated sites in the major breakpoint cluster region. 237 63

The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML.
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PMID:Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. 240 27

Although collagen myelofibrosis indicates poor prognosis in late stages of chronic myelogenous leukemia, the significance of reticulin stain-measured fibrosis in newly diagnosed patients is unknown. One hundred and thirty-eight patients with untreated or minimally treated chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia had reticulin stain studies made on their bone marrows at diagnosis. Reticulin fibrosis was graded on a scale of 1 to 4. Significant (Grade 3 or 4) fibrosis was noted in 65 patients (47%). Compared with patients with mild (Grade 1 to 2) reticulin fibrosis, those with significant fibrosis had a higher incidence of splenomegaly greater than or equal to 10 cm (29% versus 49%; P = 0.02), hemoglobin less than 10 g/dl (19% versus 49%; P less than 0.01), weight loss greater than or equal to 6.75 kg (10% versus 30%; P = 0.11), marrow blasts greater than or equal to 5% (7% versus 28%; P less than 0.01), peripheral blasts greater than or equal to 3% (30% versus 46%; P = 0.09), and additional karyotypic abnormalities (1% versus 17%; P less than 0.01). The incidence of thrombocytosis was similar in the two groups. Prognostically, median survival was significantly shorter for the 26 patients with Grade 4, compared with the 39 patients with Grade 3, and the 73 patients with Grade 1 or 2 reticulin fibrosis (32 versus 49 versus 57 months; P = 0.03). Reticulin fibrosis is a useful biologic and prognostic index in newly diagnosed patients with chronic phase chronic myelogenous leukemia.
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PMID:The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia. 243 99

Comparisons of the level of proto-oncogene expression in neoplastic cells and in normal cells are being made to determine the role of these genes in neoplastic development. Recent papers have reported that leukemic cells differ from normal cells in having higher c-myc RNA levels. One problem in interpreting these data is that leukemic and normal cell populations differ in the proportion of immature cells present in each. The studies described here, using chronic phase chronic myelogenous leukemia (CML) cells, compared the level of proto-oncogene expression in immature and mature myeloid cells. Substantial differences in the level and pattern of expression were found with the immature cells containing higher c-myc RNA levels and the mature cells containing higher histone H3 RNA levels. c-fos RNA levels parallel the distribution of monocytes. While the c-myc RNA level in the CML cell population as a whole is similar to that in normal marrow cell populations and less than that in the bone marrow cells of patients with acute myelogenous leukemia (AML), c-myc RNA levels in subpopulations of immature chronic phase CML myeloid cells approximate that found in AML cells. Additionally, the studies described here suggest that the presence of high c-myc and c-fos RNA levels in light density immature cells may be a unique characteristic of acute myeloid leukemic cells.
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PMID:Differing patterns of proto-oncogene expression in immature and mature myeloid cells. 244 85

The monocyte, monocyte conditioned media (MoCM), giant cell tumor conditioned media (GCT) and a purified colony-stimulating factor (G-CSF) promote granulocyte-macrophage progenitors (CFU-GM) growth and differentiation along the neutrophil lineage and also induce alkaline phosphatase (NAP) synthesis in the neutrophilic cells of normal subjects and of patients with chronic phase chronic myelogenous leukemia (CML). However, it is not known if granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (CSF-1) or other cytokines can induce NAP synthesis from the neutrophilic cells of CML patients. The objective of this study were (a) to ascertain which of the three CFU-GM CSFs would induce NAP synthesis, and (b) to test if any of the other cytokines--interleukin-1 (IL-1), interleukin-2 (IL-2), alpha- and gamma-interferons (alpha-INF and r-INF), and phytohemagglutinin-stimulated T-cell conditioned media (TCM) would induce NAP synthesis. Light density cells obtained from the blood of patients with chronic phase CML were depleted of T cells and monocytes. These cells were cultured with various amounts of G-CSF, GM-CSF, CSF-1, IL-1, IL-2, alpha-INF, r-INF, MoCM, GCT and TCM in a suspension culture system over 6-7 days. Evaluation of the cultures indicated that G-CSF, MoCM and GCT, but not the other factors or cytokines, consistently induced NAP synthesis in a dose-dependent manner. Actinomycin-D and puromycin in separate cultures inhibited NAP synthesis without any significant reduction in cell counts. This indicated that NAP is not prepackaged in neutrophilic cells, and its synthesis occurs by a sequential transcription at the DNA level and translation at the ribosomal level. Our results suggest that the molecule which is responsible for promotion of CFU-GM growth and differentiation along the neutrophilic cell lineage is also responsible for derepression of NAP gene and initiation of NAP synthesis.
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PMID:Granulocyte colony-stimulating factor (G-CSF) induces synthesis of alkaline phosphatase in neutrophilic granulocytes of chronic myelogenous leukemia patients. 245 37

A 31-year-old woman with Philadelphia chromosome-positive chronic myeloid leukaemia (CML) was treated intermittently with high-dose busulphan over a 6-yr period (total dose 1320 mg). 3 yr later (after receiving no further cytotoxic drugs) she developed pancytopenia and marrow aplasia of relatively abrupt onset. Transfusion of reconstituted blood-derived stem cells (collected 7 yr previously) re-established chronic phase CML. These events are more consistent with 'stem cell exhaustion' than with an acquired marrow microenvironmental defect occurring in the course of CML. The contribution of busulphan is uncertain.
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PMID:Marrow aplasia developing 3 years after treatment with busulphan for chronic myeloid leukaemia. 256 49

The monoclonal antibody (MoAb) Bsp-1 was used to purify basophilic cells from leukemic blood of five patients with Philadelphia chromosome (Ph') positive chronic myeloid leukemia (CML) and two patients with acute myeloid leukemia (AML) characterized by the chromosomal translocation t(6;9)(p23;q34). When cultured, Bsp-1 positive cells from all CML and AML patients showed the same clonal karyotype changes observed in diagnostic buffy coat preparations, indicating that the basophilic cells were of leukemic origin. In contrast, T lymphocytes from four of five CML patients cultured in the presence of interleukin-2 (IL-2) showed a normal karyotype and were therefore not derived from the leukemic clone. Bsp-1 staining correlated with toluidine blue-positive basophils in chronic phase CML and with toluidine blue-negative blast cells expressing an immature myeloid phenotype in blast crisis CML and AML. Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients. These results indicate that the breakpoint at 9q34 in CML is 5' of ABL, whereas the breakpoint at 9q34 in AML is 3' of ABL. Field inversion gel electrophoresis showed that the 9q34 breakpoint was not within 200 kb 3' of ABL in one of the AML patients, nor was there any rearrangement of the PIM oncogene locus at 6p21.
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PMID:Basophils (Bsp-1+) derive from the leukemic clone in human myeloid leukemias involving the chromosome breakpoint 9q34. 264 88

Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the presence of ras mutations using polymerase chain reaction (PCR), oligonucleotide hybridization, and direct PCR sequencing. All cases had preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes were detected in none of 39 patients with Philadelphia (Ph) chromosome or bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18 patients in blast crisis, suggesting that ras mutations have little or no role in initiation or progression of common CML. Seven of 13, or 54% of patients with bcr/abl rearrangement negative chronic phase CML (atypical CML) harbored mutations in ras, however. This high incidence of ras mutations, together with the absence of bcr/abl rearrangement, provides evidence that atypical CML is an entity that is molecularly distinct from common CML. Moreover, the clinical characteristics and the high frequency of ras mutations suggest that atypical CML may constitute a subset of the myelodysplastic syndrome and may be best classified as a variant of chronic myelomonocytic leukemia (CMML).
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PMID:Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia. 268 96

Fourteen patients with poor-risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out-patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.
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PMID:Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia. 280 80


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