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)

In the prospective study, we examined hematopoietic mixed chimerism (using polymerase chain reaction (PCR) of variable number of tandem repeat-VNTR sequences) and minimal residual disease (MRD) status (using qualitative and in the case of positivity quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the BCR/ABL fusion mRNA) in serial peripheral blood samples taken from 25 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Increasing mixed chimerism in correlation with increasing signal of MRD was detected in 10 patients. In two patients mixed chimera status and BCR/ABL rearrangement led to hematologic relapse, in five patients molecular relapse was followed by reappearance of Ph chromosome and three patients developed molecular relapse only. Adoptive immunotherapy-donor lymphocyte infusion (DLI), interferon (INF) and discontinuation of post-transplant immunosupression-separately or in different combinations was used in nine patients with molecular, cytogenetic or hematologic relapse of CML. The results demonstrate that significant response at the molecular level can be achieved for a majority of CML patients and that using of all forms of adoptive immunotherapy controlled by MC and MRD is more efficient in patients treated in early molecular relapse-with minimal disease burdens.
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PMID:Prediction and reversion of post-transplant relapse in patients with chronic myeloid leukemia using mixed chimerism and residual disease detection and adoptive immunotherapy. 1071 31

In this paper, a patient is described who presented with peripheral blood and bone marrow features uncharacteristic of chronic granulocytic leukemia, which proved to be Philadelphia (Ph) chromosome-positive by metaphase and interphase cytogenetic analyses but lacked the p210 type of BCR/ABL fusion gene mRNA product by two different sensitive RT-PCR assays. In the course of the 32-month follow-up with a termination into a myeloblastic crisis, molecular investigations were performed four times. They indicated a constantly high rate of Ph positive cells and lack of BCR/ABL mRNA expression, except in the second investigation, when the patient showed reverse transcription polymerase chain reaction positivity with b3/a2 type of chimera, fusion gene mRNA expression, and a striking change in the bone marrow histology. Our findings might indicate that the dormant Ph chromosome state may exist not only at the primitive progenitor, but also at the entire peripheral blood cell compartment level.
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PMID:Silent Philadelphia chromosome: a distinct developmental stage in a philadelphia chromosome-positive chronic myeloproliferation? 1073 84

Reverse transcription-polymerase chain reaction (RT-PCR) was used to study 34 patients with chronic myelogenous leukemia (CML) associated with negative Philadelphia (Ph) chromosome. This report showed evidence of a chimeric BCR/ABL transcript in 18 (52.9%) and 28 (82.4%) cases by first PCR and seminested PCR, respectively. In these BCR/ABL transcript positive cases, the incidence of BCR exon3/ABL exon2 (B3A2) and BCR exon 2/ABL exon2 rearrangement was 25 (89.3%) and 3 (10.7%) cases, respectively. The other 6 Ph negative patients showed no evidence of reciprocal translocation of BCR to chromosome 9. This data demonstrates that seminested PCR is sufficiently sensitive to detect BCR/ABL fusion transcript in Ph chromosome negative CML patients.
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PMID:BCR/ABL rearrangement in Philadelphia chromosome negative CML patients. 1086 10

A 21-year-old man, diagnosed in March 1997 as having chronic myelogenous leukemia (CML), received hydroxyurea followed by daily interferon (IFN) until December 1998, when the additional chromosome abnormality of +8 appeared. As no suitable matched donor was available, the patient received mobilization therapy consisting of mini-ICE (idarubicin, cytarabine, etoposide) followed by G-CSF subcutaneously. During hematopoietic recovery, a total of 12 x 10(6)/kg CD34-positive cells were harvested. Cytogenetic analysis of peripheral blood stem cell (PBSC) products using FISH revealed 1% BCR/ABL fusion signals. In March 1999, he received conditioning therapy consisting of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by infusion of 5 x 10(6)/kg CD34-positive cells. A neutrophil count of 500/microliter and a platelet count of 5 x 10(4)/microliter were attained by days 20 and 38, respectively. Bone marrow aspirates showed 2.6% BCR/ABL fusion signals on day 35 after autologous PBSC transplantation, and the patient remained in chronic phase until the sixth month, when a cytogenetic relapse (Ph, +8:4/20) occurred. These observations suggest that Ph-negative progenitor cells can be harvested using a mini-ICE regimen followed by G-CSF, and that autologous PBSC transplantation is feasible in patients with CML resistant to IFN.
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PMID:[Autologous transplantation of Ph-negative peripheral blood stem cells for treatment of chronic myelogenous leukemia]. 1102 Sep 96

Chronic myelogenous leukaemia is a clonal myeloproliferative stem cell disease. Its cytogenetical hallmark is the Philadelphia chromosome (Ph) or the BCR/ABL fusion gene. Their identification is important both in the diagnosis and the follow-up of the disease. In our department we have investigated the BCR/ABL gene arrangement in 21 patients with fluorescence in situ hybridization. The aim of the analysis in freshly suspected patients without any previous therapy was to confirm diagnosis and mapping the ratio of Philadelphia positive cells. In contrast to the 95-100% Ph-positivity of mononuclear cells by classical cytogenetical examinations we found BCR/ABL gene arrangement only in various but always lower proportions. Therefore the latter examination gives a better representation of residual normal hemopoesis. Out of 9 patients who had received interferon treatment for at least 6 months, 4 gave a major, 4 a minor cytogenetical answer and in 1 case there was no cytogenetical response. Seven patients reached a complete and 2 a partial hematological remission. Among 5 other patients receiving interferon treatment, in 2 cases with double Ph-positivity we found a rapid progression. The data of 3 patients had to be excluded from the evaluation due to the so far short following time.
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PMID:[Fluorescence in situ hybridization in the diagnosis and follow-up of chronic myelogenous leukemia]. 1102 76

In chronic myeloid leukemia, accurate determination of Ph(-) Hemopoietic stem cells (HSC) in peripheral blood (PB), bone marrow (BM) and leukapheresis products is important for the selection of patients for whom mobilization, collection, and autografting of Ph(-) HSC are envisaged. To this effect, the BCR/ABL fusion was assessed at the single cell level in 25 sets of PB and BM samples using dual-color I-FISH in immunophenotyped CD34(+) cells and RT-PCR of individual CFU-GM colonies. In 15 cases found to be 100% Ph(+), the respective BCR/ABL gene was absent in 30% of CD34(+) cells, while the respective transcripts could not be identified in 17% of CFU-GM. The mean percentage of BCR/ABL(-) CD34(+) cells and CFU-GM cells was higher (38% and 29%, respectively) in untreated patients than in treated patients (24% and 7%, respectively). In eight cases with cytogenetic response (CgR), the percentage of Ph(-) metaphases correlated with the level of BCR/ABL(-) colonies in BM and PB and with the proportion of BCR/ABL(-) CD34(+) cells in the BM. Immunophenotyping and FISH was fast, easy, always informative, and quantitative for the BCR/ABL(-) CD34(+) cells. Our results show that (a) at early diagnosis a high frequency of BCR/ABL(-) HSC circulate in the PB and that Ph(-) hematopoiesis is not completely suppressed; (b) although normal clonogenic cells decline rapidly within a few months after diagnosis, appreciable numbers of normal CD34(+) cells survive in chronic phase, especially in patients with CgR.
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PMID:Evaluation at single cell level of residual Philadelphia negative hemopoietic stem cells in chronic phase CML patients. 1110 18

Fluorescence in situ hybridization (FISH), as a new clinical test, is not presently standardized. For practical reasons, each laboratory must build its own criteria. In this work, we present our standardization criteria for clinical practice, which include not only the methods for cell fixation, specimen preparation, and hybridization conditions, but mainly the definition of false-positive range and the scoring criteria of microscopic analysis. These include signal assessment, difference between individual microscopists, evaluation of specimen homogeneity, and the minimum number of scored nuclei required for a clinically reliable result. For this purpose, we analyzed by FISH 24 healthy volunteer donors, 31 patients affected by non-chronic myelogenous leukemia (CML) hematological malignancies, 47 CML patients at diagnosis, and 82 CML patients during treatment for the BCR/ABL fusion. In this article, we present several quality control and assurance methods that can be useful in providing standardization of the FISH technique.
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PMID:Standardization criteria for the detection of BCR/ABL fusion in interphase nuclei of chronic myelogenous leukemia patients by fluorescence in situ hybridization. 1115 May 99

This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.
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PMID:Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study. 1124 96

We describe the cases of two patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL-positive CML.
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PMID:Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemia. 1128 30

An unusual cytogenetic rearrangement, described as ins(22;9)(q11;q34q21), was detected in a 49-year-old male patient diagnosed with chronic myeloid leukemia (CML). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed a b3a2 fusion transcript. In order to confirm the cytogenetic findings and fully characterize the inverted insertion, we performed fluorescence in situ hybridization (FISH) assays using locus-specific and whole chromosome painting probes. Our FISH analysis showed the presence of the BCR/ABL fusion gene, verified the insertion and determined that the breakpoint on chromosome 22 where the insertion took place was located proximal to the BCR gene and distal to the TUPLE1 gene on 22q11.
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PMID:Insertion (22;9)(q11;q34q21) in a patient with chronic myeloid leukemia characterized by fluorescence in situ hybridization. 1136 63


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