Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Seven patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with an ICE-based regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells in the setting of an autologous transplant program. Five patients had CML in the first chronic phase and 2 in the accelerated phase. All patients had been previously treated with interferon-alpha. Median value and ranges for harvested mononuclear cells, CD34+ cells and CFU-GM, respectively: 5.65 x 10(8)/kg (2.61-11.38); 1.48 x 10(6)/kg (0.216-3.5), and 3.43 x 10(4)/kg (0.243-11.6). FISH was the only useful method for detection of minimal residual disease on apheresis product showing <5% t(9;22) positive cells in 2 cases and <10% positive cells in 4 other cases. Four of seven autologous grafts have been transplanted to date. Busulfan conditioning was used in 1 case and TBI/Cy conditioning in 3 other cases. All patients are alive and well following transplantation and are on interferon-alpha therapy.
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PMID:Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia with different clinical stages. 1171 74

Chronic myeloid leukemia in a 61-year-old man progressed into the accelerated phase 8 months after the initial evaluation (Ph chromosome [20/20], FISH 93.5%), although the major cytogenetic response (Ph chromosome [0/20], FISH 9.7%) had been achieved 6 months after the initiation of the treatment with interferon and hydroxyurea. The Peripheral blood stem cells (Ph chromosome [0/20], FISH 5.8%, PCR 2.7 x 10(2) copies/microgram RNA) were harvested simultaneously with the attempt to induce the second chronic phase using the mini-ICE (idarubicin, cytosine arabinoside and etoposide) therapy. However, 2 months later, the disease progressed into blast crisis with the additional chromosomal abnormalities, and did not respond to the re-induction therapy with idarubicin and cytosine arabinoside. Autologous stem cell transplantation was then performed using the preparatory regimen with busulfan and cyclophosphamide. The third chronic phase was successfully achieved, and has been well maintained with imatinib for more than 13 months (Ph chromosome [0/20], FISH 0.0%, PCR < 10(2) copies/microgram RNA). This may be a rare case in which normal hematopoietic stem cells could be enriched in the peripheral blood in the accelerated phase, and that cytogenetic remission was achieved using these cells in the blast crisis. Flexible use of peripheral blood stem cells and imatinib could be an additional strategy for the better treatment of chronic myeloid leukemia.
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PMID:[Successful attainment of the third chronic phase by autologous peripheral blood stem cell transplantation and imatinib in a patient with chronic myeloid leukemia]. 1282 5

The detection of incomplete chromosome elements (ICE, i.e., elements with telomeric signal at only one terminal end) and interstitial fragments induced by the radiomimetic compound bleomycin (BLM) was carried out in a Chinese hamster embryo (CHE) cell line using FISH with a telomeric peptide nucleic acid (PNA) probe. CHE cells were treated with 0, 1, 2.5, 5, and 7.5 microg/ml of BLM and chromosomal aberrations were analyzed in the first mitosis after treatment using a telomeric PNA probe. The relationship between chromosomal aberrations frequency and bleomycin concentration was of linear type (P < 0.05 for all type of aberrations analyzed, i.e., multicentric chromosomes, centric rings, interstitial fragments and ICE). After BLM treatment, about 20-30% of the analyzed metaphases contained one or more pairs of ICE. Acentric interstitial fragments, lacking telomeric signals, were observed with a frequency of about 4-7 times higher than the dicentric frequency. Acentric interstitial fragments and ICE were induced at similar frequencies, except for the lowest BLM concentration (1 microg/ml), where the latter ones showed a higher frequency than the former ones. Furthermore, it was estimated that about 53% of excess acentric fragments originate from complete exchanges (interstitial deletions) and 47% from incomplete exchanges or terminal deletions. These results show that interstitial fragments and ICE are the most frequent asymmetrical chromosomal aberrations induced by BLM and indicate that true incompleteness is a common event following exposure to BLM. Moreover, the comparable trend of the concentration-response relationship for the different aberrations strongly suggests that all BLM-induced asymmetrical aberrations are formed by a similar underlying mechanism.
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PMID:Detection of incomplete chromosome elements and interstitial fragments induced by bleomycin in hamster cells using a telomeric PNA probe. 1545 Mar 98

Herein, we aimed to report a diffuse large B cell lymphoma (DLBCL) case that had extensive cutaneous relapse with no skin involvement previously. A 59-year-old man presented to hospital in April 2014 with fatigue, anorexia, fever, and anemia. Cervical lymph node biopsy revealed CD20+, BCL2+, MUM1+, BCL6+ high grade B lymphoproliferative neoplasm. After FISH investigation, he was diagnosed as DLBCL. He was given 7 cycles of R-CHOP and achieved remission. However, in November 2014, he had emerging skin lesions that cover nearly all of his body. A control PET-CT revealed diffuse cutaneous involvement. CD20+, BCL2+, MUM1+, BCL6+ high grade B cell lymphoma infiltration was detected with skin biopsy. He was diagnosed as relapse lymphoma, so 2 cycles of R-DHAP were given. There was no treatment response; therefore, R-ICE regimen was started. The patient had achieved second complete remission and his skin lesions were completely regressed. The involvement of skin with CD20+ cells after 7 cycles of rituximab therapy favors that there is a rituximab resistant disease which tends to involve the skin. To conclude, DLBCL may relapse extensively with cutaneous involvement and the best treatment option in these patients is salvage chemotherapy followed by autologous peripheral blood stem cell transplantation.
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PMID:Diffuse Large B Cell Lymphoma with Extensive Cutaneous Relapse. 2645 84