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)

The membrane phenotype of leukaemic cells was analysed during different stages of chronic myeloid leukaemia by a panel of markers. These included antisera against ALL antigen, p23,30 (Ia-like structure) and other T cell, B cell and myeloid markers 'Lymphoid' blast crisis shares the phenotype of common ALL (of non-T, non-B variety). Both leukemias react with anti-ALL serum and have pre-myeloid, pre-B lymphoid and pre-thymocyte characteristics. Their phenotype may reflect the characteristics of the pluripotential stem cell from which they derive. Nevertheless both leukaemias retain their undifferentiated characteristics and lack overt myeloid, B cell and thymocyte differentiation markers. Myeloid blast crisis and AML are negative with anti-ALL serum but some of the poorly differentiated myeloblasts react with anti-p23,30 serum (and negative for SmIg). The anti-p23,30 serum (used in a double marker assay combined with anti-immunoglobulin) detects some (4-11%) intermediate sized agranular p23,30+/SmIg-cells in peripheral blood during the chronic phase of CML as well as in normal foetal bone marrow. These could be myeloid stem cells (from which in CML the myeloid blast crisis arises). The results demonstrate that surface membrane analysis can aid exact diagnosis in different stages of CML.
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PMID:Membrane marker analysis of 'lymphoid' and myeloid blast crisis in PH1 positive (chronic myeloid) leukemia. 30 6

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.
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PMID:The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. 158 43

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

The cytogenetic, hematologic, and clinical characteristics of a 13-year-old girl with acquired t(6;9)(p23;q34) and dysmyelopoietic syndrome developing into acute myelomonocytic leukemia are described, bringing the total number of patients with t(6;9) and hematologic disease described in the literature up to 19. The diagnosis has been acute myeloid leukemia in the great majority of these patients; only four have had acute myelomonocytic leukemia. High resolution analysis at the 550 band stage localized the breakpoints in chromosomes #6 and #9 to p23 and 9q34.3, respectively. Previous investigations employing high resolution cytogenetics have mapped the typical 9q breakage site in chronic myeloid leukemia to 9q34.1. In situ hybridization studies have demonstrated that the cellular oncogene c-abl remains on the derivative 9q+ chromosome in t(6;9), whereas it is moved to the Ph marker in t(9;22). Thus, the combined data indicate that c-abl is located between 9q34.1 and 9q34.3, i.e., in subband 9q34.2 or its immediate vicinity.
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PMID:High resolution banding analysis of the reciprocal translocation t(6;9) in acute nonlymphocytic leukemia. 345 23

This article documents the cytogenetic findings in 79 patients with typical Ph-positive chronic myelocytic leukemia (CML). Direct preparations of bone marrow and/or peripheral blood of 46 males and 33 females were studied with different banding techniques. Seventy patients were studied during chronic phase. Three (4.3%) had unusual or complex translocations: t(6;22)(p21;q11), t(8;12;9;22)(p21;q21;q34;q11), and t(9;11;22)(q34;q13;q11). One (1.4%) had a +Ph, 1 (1.4%) had a +8, 1 (1.4%) had a del(3)(p13,p23), and 4 of 30 males (13.3%) showed loss of Y chromosome. Five of 8 cases studied during blast crisis had additional abnormalities. The +8 occurred in 4 cases, +10 and +19 each in 3 cases, +6, + 9q+, and +13 each in 2 cases, and +5, +11, +14, +21, +Ph, i(17q), dic(1;9), and structural abnormalities of chromosomes #1, #5, #12, and #13 each in 1 case. Two cases studied in blast crisis alone had complex translocations leading to the Ph. Because it cannot be ruled out that these translocations are secondary, they were not included in the calculation of the frequency of atypical translocations.
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PMID:Philadelphia chromosome (Ph) positive chronic myelocytic leukemia (CML): frequency of additional findings. 385 71

Acute nonlymphocytic leukemia associated with the chromosomal translocation t(6;9)(p23;q34) is an entity that is frequently associated with basophilia, which it shares with chronic myelogenous leukemia. The breakpoint on chromosome 9, q34, appears to be cytogenetically identical in both malignancies and is the site of the cellular oncogene c-abl. We investigated the role of c-abl in cells from two patients with the t(6;9) using in situ chromosomal hybridization, Southern hybridization, and in vitro phosphorylation. We showed that c-abl is not translocated from chromosome 9, resulting in a breakpoint that is on the 3' side of this gene. The t(6;9) translocation does not appear to result in the production of an aberrantly sized protein product or in the acquisition of in vitro tyrosine kinase activity. This is in direct contrast to the findings in chronic myelogenous leukemia, in which c-abl is translocated, leading to the production of a structurally altered c-abl protein with activated tyrosine kinase. Lastly, we demonstrated that the cells of one patient contain sequences from chromosome 9 inserted at the junction of a reciprocal translocation between chromosomes 4 and 10 on the 4q+ chromosome. This insertion, which is at least 100 kilobase pairs in length, represents a duplication and translocation of the protein coding region of c-abl.
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PMID:Chromosomal localization and characterization of c-abl in the t(6;9) of acute nonlymphocytic leukemia. 386 48

We have characterized another subset of acute nonlymphocytic leukemia (ANLL) based on the cytogenetic and morphologic findings in a group of nine patients. Five patients had chromosomal analyses performed at the University of Chicago, two patients were studied at the All-Union Cancer Research Center in Moscow, and one patient each was studied at the University of Maryland and at Fairfax Hospital in Fairfax, Virginia. All nine patients had a reciprocal translocation involving the short arm of chromosome 6 and the long arm of chromosome 9 [t(6;9)(p23;q34)]. The patients, four males and five females, ranged in age from 5 to 51 years; the median age of 38 years is lower than that typically seen in ANLL. Only two of eight treated patients entered a complete remission. Classification of bone marrow morphology according to FAB Cooperative Group criteria revealed AML-M1 in one patient, AML-M2 in four, and AMMoL-M4 in three. One patient had refractory anemia with excess blasts (RAEB) which evolved to AML-M2. All bone marrow specimens showed severe myelodysplasia, with Auer rods present in seven of the nine cases. Of note was the particular prominence of bone marrow basophils (greater than 1%) in eight of the nine (89%) patients. Among 160 evaluable patients with ANLL de novo seen at the University of Chicago whose cells lacked a t(6;9), only five (3%) had greater than 1% basophils in the marrow aspirates. It is of interest that the breakpoint in 9q involves the same chromosomal band as that in the t(9;22) observed in chronic myelogenous leukemia (CML), in which increased basophils are a prominent feature. Thus, the association of the t(6;9) with increased bone marrow basophils in ANLL may provide additional insight into the chromosomal location of genes regulating the production and/or maturation of basophils.
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PMID:Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL. 397 50

We report the molecular cytogenetic analysis of a case of Philadelphia (Ph)-negative, BCR-positive chronic myeloid leukemia (CML) which appeared by conventional cytogenetics to have a t(6;9)(p23;q34) as the sole cytogenetic abnormality. Neither conventional nor pulse-field Southern blots detected any rearrangement of the DEK or CAN genes which are often fused in acute myeloid leukemia (AML) with t(6;9)(p23;q34). However, rearrangements of both BCR and ABL genes were detected. The breakpoint in BCR was located in the major translocation cluster region between exons b1 and b3. ABL rearrangements were detected with an ABL exon 1B probe and with a probe located 5' of the entire ABL gene. Comigration between the rearranged fragments obtained with M-bcr-5' and ABL exon 1B probes was observed, implying that the entire ABL gene was fused to the 5' part of the BCR gene. Fluorescence in situ hybridization (FISH) analyses using BCR and ABL probes showed that in 20% of metaphases BCR and ABL signals were present on one chromosome 6 at 6p23, whilst in 80% of metaphases BCR and ABL signals were identified on both copies of chromosome 6. Furthermore, FISH analysis with a whole-chromosome 22 paint demonstrated that chromosome 22 material was present on both copies of chromosome 6. These data indicate a complex Philadelphia translocation involving chromosome band 6p23 and duplication of the whole aberrant chromosome. The nature of the gene locus on 6p23, involved in this rearrangement, remains unknown. A similar translocation has been previously reported in a case of CML, which also lacked DEK and CAN gene rearrangements implying that abnormalities of 6p23 involving genes other than DEK may be a recurrent abnormality in CML.
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PMID:Molecular cytogenetics of chronic myeloid leukemia with atypical t(6;9) (p23;q34) translocation. 759 89

A 57-year-old female was diagnosed being in the blastic phase of chronic myelogenous leukemia (CML) on her second admission in May 1993. The patient was previously treated with vincristine and prednisolone in the accelerated phase of CML in December 1991 without improvement. Other chemotherapeutic agents such as BHAC-DMP (enocitabine, daunorubicin, mercaptopurine, prednisolone), interferon, mercaptopurine and ranimustine were also administered. After the second chronic phase was achieved, she was treated with busulfan as an outpatient. On her second admission, the diagnosis of erythroblastic transformation was made, and cytogenetic study revealed t(9;22) (q34;q11) with the additional chromosomal abnormalities, t(6;9) (p23;q34). This karyotype rearrangement has been reported neither in Ph-positive CML nor in blastic crisis.
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PMID:[Erythroblastic transformation of chronic myelogenous leukemia associated with an additional chromosome abnormality translocation (6;9]. 869 72

Several important signaling proteins including transcription factors and protein kinases depend on heat shock protein (Hsp)-90 for stability. p210bcr-abl, a protein expressed in chronic myelogenous leukemia, is functionally inhibited by the benzoquinone ansamycin herbimycin A. Benzoquinone ansamycins also bind to and inhibit the activity of Hsp90. We now demonstrate that p210bcr-abl is complexed with Hsp90 and its cochaperone p23 in K562 chronic myelogenous leukemia cells. Brief exposure to the benzoquinone ansamycin Hsp90 inhibitor geldanamycin (GA) decreases the association of p210bcr-abl with Hsp90 and p23 and increases its association with the chaperones Hsp70 and p60Hop. GA has a similar effect on chaperone association with v-src, another Hsp90-dependent oncogenic kinase. Loss of Hsp90/p23 association and acquisition of Hsp70/p60Hop association of both p210bcr-abl and v-src precede GA-induced degradation of these kinases. GA-induced degradation is mediated by the proteasome because proteasome inhibitors block the effects of GA, causing both p210bcr-abl and v-src to accumulate in a detergent-insoluble cellular fraction. Both p210bcr-abl and v-src are more susceptible to GA-induced degradation than are their normal cellular counterparts, c-abl and c-src.
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PMID:The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome. 1093 89


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