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)

Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.
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PMID:Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia. 135 2

The Philadelphia chromosome (Ph1) was the first genetic change to be associated consistently with leukemia, and it is one of the best understood on the molecular level. Because of this, it is an excellent model to investigate the application of molecular techniques to the clinical setting. These techniques are reviewed as are their clinical use in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and transplantation. The Ph1 is caused by the fusion of two genes on chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. This new gene is believed to be the cause of these Ph1-positive leukemias. The ability to detect the BCR-ABL fusion gene evolved from cytogenetic detection to Southern blot analysis, and now includes sophisticated techniques such as polymerase chain reaction (PCR) methods and pulsed-field gels. Diagnosis of the BCR-ABL fusion gene by Southern blot detection of bcr genetic rearrangements is the prototype of molecular cancer diagnosis. The sensitivity and clinical uses of this test are reviewed, especially its application to monitoring the response to treatment. PCR methods enable the researcher to detect 1 CML cell in a population of 10(5) cells. Clinical experience with PCR, especially in transplantation medicine, is providing a better understanding of the meaning of the terms "remission" and "cure." Newer techniques using fluorescent in situ hybridization have considerable potential for BCR-ABL detection, but no clinical experience has been gained with these techniques currently. The diagnosis of the BCR-ABL fusion gene in ALL has important clinical implications because it is the most common molecular genetic change in adult ALL and is associated with short remissions and poor outcome in all age groups. Diagnosis of the BCR-ABL fusion in ALL is difficult because the molecular findings are more heterogeneous than they are in CML. The methods available and their accuracy and sensitivity are compared. A review of their clinical impact is included.
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PMID:The role of molecular techniques in the clinical management of leukemia. Lessons from the Philadelphia chromosome. 151 23

The Philadelphia (Ph) translocation is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL) and is associated with an adverse prognosis. Using polymerase chain reaction (PCR) technology we recently observed a remarkably high incidence (55%) of BCR-ABL rearrangements in adult common ALL patients. In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR-ABL transcripts. PCR analysis of 58 adult Ph-negative cALL patients, including 47 cases with a normal karyotype revealed no evidence of chimeric BCR-ABL genes. We conclude that Ph-negative BCR/ABL-positive ALL is very rare entity if existing at all.
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PMID:Polymerase chain reaction analysis of BCR-ABL sequences in adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. 159 11

The CML-specific Philadelphia (Ph1) chromosome is relatively common cytogenetic abnormality of ALL, which has been shown 20% of adult ALL and 5% of child ALL. We analysed here the 12 patients of Ph1-positive ALL, aged 35 to 69-years old, who were experienced in our hospital for latest eight years. In comparison with Ph1-negative ALL, these 12 patients were elder and showed high peripheral and bone marrow leukemic cell counts. Of these, seven patients had 100% Ph1 abnormality in the bone marrow and another five patients showed mosaic marrow patterns of Ph1 and normal chromosomes. Remissioned eight cases had no more Ph1 abnormalities in their bone marrows. Our Ph1-positive ALL revealed B-cell lineage leukemia, since their surface phenotype were Ia+ and CD10+ and they have rearranged immunoglobulin JH genes. Four out of these nine patients had such gene rearrangement in the 5.8kb bcr (major BCR: M-BCR) as CML's patient had. Eight out of twelve Ph1-positive ALL patients (66.7%) achieved complete remission, but the prognosis was so bad since they had shorter remission duration (median 6.7 mos) and survival months (median 11.9 mos) than those of Ph1-negatives.
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PMID:[Philadelphia chromosome-positive adult acute lymphocytic leukemia]. 206 78

The presence of Philadelphia chromosome t(9:22) is a hallmark of 95% of clinical cases of chronic myelogenous leukemia (CML) as well as 20% of adult acute lymphoblastic leukemia (ALL) and 5% of acute myeloid leukemia (AML). The product of t(9;22) is a fusion protein BCR-ABL. The fusion proteins of CML, ALL and AML have increased tyrosine kinase activity and show a transforming potential in vitro and in animal models. The shorter p190 protein is associated almost only with ALL and AML, while the protein p210 is present in both chronic phase and blast crisis of CML and also in 50% of Philadelphia-positive (Ph1+) ALL. In CML the transition from chronic phase to blast crisis is usually accompanied by additional genetic events, e.g. additional chromosomal abnormalities, and oncogene activation(s). The detailed understanding of molecular basis of CML, and Ph1+ ALL and AML provides highly sensitive molecular and serological methods to complement classical cytogenetics. The advantages and limitations of these techniques are described and discussed below.
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PMID:Molecular pathology of chronic myelogenous leukemia. 224 53

Recently, treatment of leukemia has shown remarkable progress. Development of new antileukemic drugs, improvements in supportive care and rapid progress in bone marrow transplantation have resulted in considerable changes in responses in refractory leukemia. Chemotherapy for Acute leukemia: By the introduction of Mitoxantrone and etoposide and a new combination chemotherapy including them, a high remission rate of acute leukemia is obtained, but because of the high relapse rate the 5-year survival rates in our center were 20% for adult ALL and 18% for ANL. In order to reduce the relapse rate, a new regimen containing intensive consolidation treatments is now being studied in a nation-wide cooperative study. BMT: In 1987, 160 BMTs including 75 acute leukemia and 28 CML, were registered in Japan. The improvements in the management of graft versus host disease (GVHD) and infections in the granulocytopenic period has contributed to the marked increase in the long-term survival rate after BMT. In our center the long-term survival rate rose from 20% before 1984 to 85% after 1985. Colony stimulating factor: Macrophage-colony stimulating factor (M-CSF) and granulocyte colony stimulating factor (G-CSF) were studied in Japan. In the double-blind placebo controlled study of M-CSF, a significantly shorter duration of granulocytopenia, as well as a significantly lower rate of failure of BMT (i.e., death or retransplant) was observed. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy or BMT and marked efficacy on infection in granulocytopenic patients were observed.
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PMID:[Multidisciplinary treatment of leukemia]. 265 20

In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph') chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph'-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph'-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph'-translocation. Within the group of Ph'-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL.
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PMID:The bcr gene in Philadelphia chromosome positive acute lymphoblastic leukemia. 293 Aug 39

To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG-positive) for beta-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p less than 0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with cALL (0.6 +/- 0.3) was significantly lower (p less than 0.01) than in the group of children with cALL (1.1 +/- 0.2) or in the lymphoid-crisis group (1.5 +/- 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL-/TdT+) and the other with more (cALL+/TdT+). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The beta-glucuronidase patterns indicate a further heterogeneity in adult ALL.
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PMID:A comparative study of immunological and cytochemical profiles between adult and childhood acute lymphoblastic leukemias (ALLs): heterogeneity in adult common ALL. 293 63

Chronic granulocytic leukemia (CGL) developed in a 31-year-old man after he underwent a third renal transplant. The leukemia was initially controlled with azathioprine sodium and prednisone therapy, but eventually it entered blast cell crisis. This was controlled with an adult acute lymphocytic leukemia protocol with an excellent response. Despite discontinuing treatment with azathioprine and with the use of busulfan to control the peripheral WBC count, the patient maintained stable renal function for one year following treatment of the blast cell crisis and subsequently died of sepsis. We suggest that CGL after renal transplantation is similar to that observed in the general population and can be treated with the usual chemotherapeutic agents for the disorder without sacrificing renal function.
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PMID:Chronic granulocytic leukemia after renal transplantation. 635 25

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.
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PMID:Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation. 636 29


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