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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonogenic murine B cell precursors are normally ultrasensitive to apoptosis following genotoxic exposure in vitro but can be protected by expression of an E mu-BCL-2 transgene. Such exposures are likely to be mutagenic. This in turn suggests that a level of in vivo genotoxic exposure that usually has minimal pathological consequences might become leukaemogenic when damaged cells fail to abort by apoptosis. If this were to be the case, then the cell type that becomes leukaemic and the chromosomal/molecular changes that occur would also be of considerable interest. We tested this possibility by exposing E mu-BCL-2 and wild-type mice of differing ages to a single dose of X-irradiation of 1-4 Gy. Young (approximately 4-6 weeks) transgenic mice developed leukaemia at a high rate following exposure to 2 Gy but adult mice (4-6 months) did not. Exposure to 4 Gy produced leukaemia in both young and adult transgenic mice but at a higher frequency in the former. Leukaemic cell populations showed clonal rearrangements of the IGH gene but in most cases analysed had immunophenotypic features of an early B lympho-myeloid progenitor population which has not previously been recorded in radiation leukaemogenesis. Molecular cytogenetic analysis of leukaemic cells by banded karyotype and FISH revealed a consistent double abnormality: trisomy 15 plus an interstitial deletion of chromosome 4 that was confirmed by LOH analysis.
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PMID:An E mu-BCL-2 transgene facilitates leukaemogenesis by ionizing radiation. 1044 50

To analyze the value of real time RT-PCR for monitoring of bcr-abl expression in CML patients after allogeneic or autologous stem cell transplantation (SCT), we generated pairs of PCR-primers and TaqMan probes specific for either the b2a2- or the b3a2-variant of bcr-abl. Either variant could be detected specifically from cDNA from a single K562 (b3a2) and BV173 (b2a2) cell with the respective TaqMan probe. Bcr-abl expression was normalized by comparison with GAPDH expression, and samples were quantitated using standard cDNA dilutions from K562 or BV173 cells. In a retrospective analysis 13 patients with CML after allogeneic (n = 10) or autologous (n = 3) SCT including patients with relapsed or persistent CML were analyzed by both real-time and conventional nested RT-PCR. In addition chimerism was monitored by FISH analysis of sex chromosomes in three patients with relapsed disease. The bcr-abl/GAPDH ratio dropped at least 1000-fold in all seven patients evaluable prior to and after allogeneic SCT as estimated by real-time RT-PCR, and conventional RT-PCR became negative in 6/7 patients. In five patients with relapsed or persistent disease after allogeneic SCT the bcr-abl/GAPDH ratio eventually increased again, and real-time RT-PCR was as sensitive as conventional RT-PCR for detection of bcr-abl. Donor lymphocyte infusions (DLI) were given to all five patients, and the bcr-abl/GAPDH ratio dropped to undetectable levels in two patients both remaining in continuing molecular remission. In contrast, in three other patients the bcr-abl/GAPDH ratio decreased only or did not change significantly after DLI. In three patients undergoing autologous SCT the bcr-abl/GAPDH ratio dropped only 1.1 to 30-fold, and the patients were tested positive with real-time RT-PCR at all time points. These data demonstrate that real-time RT-PCR is valuable to quantitate bcr-abl expression in CML patients after transplantation.
Leukemia 1999 Sep
PMID:Monitoring of BCR-ABL expression using real-time RT-PCR in CML after bone marrow or peripheral blood stem cell transplantation. 1048 89

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.
Leukemia 1999 Nov
PMID:Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias. 1055 51

The MLL gene on chromosome 11 band q23 is frequently involved in chromosome translocations in acute lymphoblastic leukemia and acute myeloid leukemia. The translocation results in the formation of a fusion gene on the derivative 11 chromosome consisting of the 5' part of the MLL gene and the 3' part of another gene; already more than 30 different partner chromosome regions have been described. MLL gene rearrangements are generally correlated with a poor prognosis. Therefore the presence of an 11q23 aberration has direct implications for treatment stratification, making early and rapid detection of utmost importance. In this study, we developed a FISH probe set for detection of MLL gene rearrangements according to strict design criteria. The cosmid probes are derived from the flanking regions of the MLL breakpoint region on chromosome 11 and when used in dual colored FISH experiments give rise to a split of the normally colocalizing (fused) signals in case of a translocation. This split signal was observed in seven out of 10 cases with an 11q23 translocation with various partner chromosomes. In the three other cases, a deletion of the 3' part of the MLL gene, downstream of the breakpoint region was also found. A low false positive value of only 1.7% was obtained for interphase cells in contrast to conventional dual colored FISH where the creation of a fusion signal has cut off values of at least 5-10%. A major advantage of our type of probe set is the application of a single FISH experiment to detect all types of MLL translocations. Moreover, since this cosmid probe set can be used for either interphase or metaphase studies, metaphases are no longer a prerequisite for detecting the presence of an 11q23 translocation. Nevertheless, metaphase FISH with the new probe set is helpful in determining the partner chromosome and therefore may lead to the identification of new partner genes.
Leukemia 1999 Dec
PMID:Rapid and sensitive detection of all types of MLL gene translocations with a single FISH probe set. 1060 37

We encountered a 44-year-old woman with suspected chronic myelocytic leukemia (CML) in the acute phase that was difficult to be differentiate from Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). At disease onset, her bone marrow showed an increase in blasts that were negative for myeloperoxydase (MPO) and Positive for CD10, 19, 34, and HLA.DR. Standard type Ph was detected by chromosome analysis, and both major and minor BCR/ABL m-RNA were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) methods. Neutrophil alkaliphosphatase (NAP) score was normal, and neither eosinophilia nor basophilia was observed in peripheral blood. Under a presumptive diagnosis of Ph-positive ALL (L2), the patient was given AdVP (doxorubicin, vincristine, and prednisolone) therapy followed by a regimen of LMVP (L-asparaginase, mitoxantrone, and VP), and obtained a complete remission 2 months later. At that time, FISH analyses of her bone marrow and blood cells no longer detected bone marrow Ph or BCR/ABL fusion gene. A month later, however, the leukemia relapsed with an increase in MPO-positive blasts in bone marrow, and the patient died soon thereafter. We finally concluded that her leukemia was not Ph-positive ALL, but CML in the acute phase at disease onset.
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PMID:[Blast crisis of chronic myelocytic leukemia that was difficult to differentiate from Ph+ acute lymphoblastic leukemia]. 1062 28

Dystroglycan is a laminin binding protein, which provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix. It is also involved in the organization of basement membranes. So far the genomic organization of the dystroglycan gene DAG1 has not been completely investigated. Here we report the cloning and sequencing of 162 kb of dog genomic DNA containing the complete approximately 71-kb canine DAG1 gene, which consists of three exons, with the translation start codon located in exon 2. Its 2679-nucleotide ORF encodes a polypeptide of 892 amino acids, which is highly similar to human, rabbit, and bovine orthologs. To further characterize the dog DAG1 gene we determined the transcription start site and several naturally occurring polymorphisms, which partially result in amino acid substitutions of the dystroglycan protein. The dog DAG1 gene was assigned to chromosome 20q15.1-q15.2 by FISH analysis. The analysis of the entire reported sequence revealed that the genes for aminomethyltransferase (AMT), bassoon (BSN), TCTA (T-cell leukemia translocation-associated) gene, and an as yet uncharacterized protein are located very close to the DAG1 gene. Therefore, this study defines a novel syntenic region among dog chromosome 20q15, human chromosome 3p21, and murine chromosome 9F.
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PMID:Genomic organization of the dog dystroglycan gene DAG1 locus on chromosome 20q15.1-q15.2. 1072 May 70

Hematopoietic disorders can be used as a suitable tool of additional information on the actual resolving power of comparative genomic hybridization (CGH). Therefore, CGH examination was performed of DNA extracted from 23 acute and 15 chronic myeloproliferative disorders which had just been analyzed using classical cytogenetic techniques. In nearly all cases CGH analysis was repeated with reversely labeled probes. A Zeiss axioplan microscope was equipped with the ISIS 3 system for photometric evaluation of the CGH data. A main group was selected of 34 cases showing karyotypic mosaics when routinely diagnosed by classical cytogenetics. The grade of mosaicism was basically determined from the classical cytogenetic analysis and was additionally defined examining target anomalies by I-FISH analysis in 28 of the cases. The second group included 23 cases with deletions, and in 1 case another informative genomic imbalance could be analyzed. Every target anomaly irrespective of its type could be detected in all cases with an affected cell population equalling or exceeding about 25%, but in none was it below 23%. This value was the lowest and was found in a case, with CGH-detected 20q deletion. The smallest deletions of two bands on 20q which could visually be detected by CGH were estimated in the range of 5-7 Mb. CGH was also suitable to detect imbalances which were not clearly detected by routine cytogenetics. Reverse labelling, performed in nearly all cases, confirmed the result of the original CGH analysis. These data not only document the readiness and reliability of CGH studies on human leukemia, but also further contribute to a clearer definition of the limits of the resolving power of this technique.
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PMID:Delimiting the use of comparative genomic hybridization in human myeloid neoplastic disorders. 1081 80

Trephine biopsy evaluation in patients who have undergone high dose chemotherapy with stem cell infusion performed by an experienced pathologist is important in evaluation of hematopoietical restitution, evaluation of complications such as graft rejection, infections, relapse or secondary neoplasms. In the first week after high dose chemotherapy or radiotherapy bone marrow aplasia is evident. In the case of accompanying myelofibrosis, fragmentation of reticular and collagen fibers is noticeable only following stem cell transplantation. The first precursors, which appear after the second or third week after transplantation are erythroid precursors found in small groups. Promyelocytes and myelocytes are observed between the second and fourth week, the ration off erythroid to myeloid populations at that time is 1:1. Megakaryocytes ate the last precursors to appear. Trephine biopsy evaluation is useful in diagnosis of graft rejection, especially in case of a discrepancy between the blood morphology examination and bone marrow cellularity. Granuloma formation is an unspecific finding, which requires diagnosis of infections. Residual disease can be recognized in histopathologic examination, or sooner, with immunophenotyping, cytogenetic examination using FISH or PCR. Secondary neoplasms to high dose radiotherapy or chemotherapy are usually lymphoproliferative processes connected with latent EBV infections, myelodysplastic syndromes and acute myeloblastic leukaemia.
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PMID:Bone marrow pathology after bone marrow transplantation. 1082 96

Spectral karyotyping (SKY) was performed in patients with acute myeloid leukemia (AML; n = 25), secondary AML (s-AML; n = 7), myelodysplastic syndrome (MDS; n = 6) and s-MDS (n = 1) to complement conventional cytogenetic investigations. According to the results of conventional cytogenetics the patients were subdivided into three groups: group 1, normal karyotype, n = 19 cases, median age = 64 years; group 2, patients displaying either one or two single aberrations, n = 10 cases, median age = 54 years; group 3, patients with > or =3 independent aberrations, n = 10 cases, median age = 61.5 years. SKY identified no abnormal metaphases in group 1. In one patient of group 2 a hidden translocation t(7;14)(q3?1;q2?2) could be revealed with SKY. Conventional cytogenetics had only shown trisomy 8. A similar t(7;14) was also detected in one patient of group 3. SKY was helpful for the delineation of marker chromosomes and additional material. Furthermore, SKY could distinguish between partial and total monosomies or real existing and apparent deletions. The combination of G-banding, FISH and SKY was found very useful for the precise delineation of the karyotype. As a result of our study we recommend SKY investigation as an important additional tool for accurate chromosome analysis. The detected t(7;14) might represent a novel recurrent translocation in acute myeloid leukemias.
Leukemia 2000 Jun
PMID:Comparison of spectral karyotyping and conventional cytogenetics in 39 patients with acute myeloid leukemia and myelodysplastic syndrome. 1086 69

This study was undertaken to develop a reliable method to enumerate and map somatically acquired, clonal, murine leukemia virus (MuLV) proviral insertions in acute myeloid leukemia (AML) cells from the BXH-2 mouse strain. This was achieved by using fluorescence in situ hybridization combined with tyramide signal amplification (FISH-TSA) and an 8.8 kilobase pair (kb) full-length ecotropic MuLV or 2.0 kb MuLV envelope (env) gene probe. Two-color FISH was utilized combining chromosome-specific probes for regions near the telomere and/or centromere and the MuLV probes. The technique reliably detected germline and somatically acquired, tumor-specific, MuLV proviruses in BXH-2 AML cell lines. It was possible to readily verify homozygous insertions at endogenous ecotropic MuLV loci, Emv1 (chromosome 5), Emv2 (chromosome 8) and a BXH-2 strain-specific locus (chromosome 11). This strategy also verified the presence of molecularly cloned proviral insertions within the mouse Nf1 gene and another locus on distal chromosome 11, as well as on chromosome 7 and chromosome 9 in BXH-2 AML cell line B117. The technique was also used to detect several new tumor-specific, proviral insertions in BXH-2 AML cell lines.
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PMID:Detection of integrated murine leukemia viruses in a mouse model of acute myeloid leukemia by fluorescence in situ hybridization combined with tyramide signal amplification. 1095 40


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