Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This case report describes 2 patients with chronic myeloid leukemia in whom hemolytic uremic syndrome developed while being treated with interferon-alpha and hydroxycarbamide. Hemolytic uremic syndrome was recognized by progressive renal dysfunction, thrombocytopenia, microangiopathic hemolytic anemia, and histologic features of thrombotic microangiopathy in the kidney. Although renal dysfunction progressed to dialysis-dependent renal failure in one patient despite treatment with prednisolone and plasmapheresis but not in other, withdrawal of the treatment resulted in a prompt resolution of thrombocytopenia and microangiopathic hemolytic anemia in both patients.
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PMID:Withdrawal of interferon-alpha results in prompt resolution of thrombocytopenia and hemolysis but not renal failure in hemolytic uremic syndrome caused by interferon-alpha. 1261 3

Although hemodialysis has permitted long-term survival of patients with renal failure, beta 2 microglobulin-derived amyloidosis is a serious complication occurring most commonly in long-term hemodialysis patients. Orthopedic manifestations are quite common, but cutaneous and lingual manifestations are relatively uncommon. We report a 56-year-old patient with lichenoid plaque type of skin eruptions and lingual papules caused by beta 2 microglobulin-derived amyloidosis. Immunohistochemical study showed that amyloid deposits were positive for anti-beta 2 microglobulin antibody, but negative for anti-advanced glycation end products antibody (anti-CML and CLE antibody). We discuss the histological and the clinical features of skin manifestations of beta 2 microglobulin-derived amyloidosis.
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PMID:Cutaneous and lingual papules as a sign of beta 2 microglobulin-derived amyloidosis in a long-term hemodialysis patient. 1294 22

A direct binding site for the Grb2 adapter protein is required for the induction of fatal chronic myeloid leukemia (CML)-like disease in mice by Bcr-Abl. Here, we demonstrate direct binding of Grb2 to the Tel-Abl (ETV6-Abl) fusion protein, the product of complex (9;12) chromosomal translocations in human leukemia, via tyrosine 314 encoded by TEL exon 5. A Tel-Abl point mutant (Y314F) and a splice variant without TEL exon 5 sequences (Deltae5) lacked Grb2 interaction and exhibited decreased binding and phosphorylation of the scaffolding protein Gab2 and impaired activation of phosphatidylinositol 3-kinase, Akt, and extracellular signal-regulated kinase/mitogen-activated protein kinase in hematopoietic cells. Tel-Abl Y314F and Deltae5 were unable to transform fibroblasts to anchorage-independent growth and were defective for B-lymphoid transformation in vitro and lymphoid leukemogenesis in vivo. Previously, we demonstrated that full-length Tel-Abl induced two distinct myeloproliferative diseases in mice: CML-like leukemia similar to that induced by Bcr-Abl and a novel syndrome of small-bowel myeloid infiltration endotoxemia and hepatic and renal failure. Lack of the Grb2 binding site had no effect on development of small bowel syndrome but significantly attenuated the induction of CML-like disease by Tel-Abl. These results suggest that direct binding of Grb2 is a common mechanism contributing to leukemogenesis by oncogenic Abl fusion proteins.
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PMID:A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase. 1514 64

The involvement of radical stress has been suggested as a cause for complications in patients on dialysis, such as arteriosclerosis, dialysis-related amyloidosis, etc. It has been reported that the increase in radical stress is not only seen in renal failure, but that its amplified effect is also seen in the process of blood purification. Our group has reported on the radical stress-reducing effect of HDF. We performed four types of blood purification (HD; on-line HDF; pre, on-line HDF; post, P/P HDF) in patients on maintenance dialysis using the polysulfone (APS) dialyzer. The change in radical related markers such as pentosidine (total, free) and CML (total, free), and the CTL/Cr ratio, and the hydroperoxide radicals were studied. In HDF (post, pre), the amplification rate of hydroperoxide radicals was significantly low, whereas the reduction rate of CTL/Cr ratio as index for hydroxy radicals was significantly higher in on-line HDF than in HD. Both the total CML and T-pentosidine increased in HD but showed a decrease in HDF. As HDF uses large amounts of replacement solution, the following effects can be expected: (a) suppression of the amplification of hydroperoxide radicals and suppression of the amplification of hydroxy radicals, and (b) suppression of fat oxidation by AGEs themselves. These antiradical stress effects are presumed to be exerted by effective removal of radical carrier protein, denatured protein, and complement protein in HDF, by dilution of radicals by massive use of replacement solution, and by the sequential reduction of the excitation and amplification effects.
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PMID:Effect of hemodiafiltration against radical stress in the course of blood purification. 1565 28

A 59-year-old woman, diagnosed with chronic myelogenous leukemia (chronic phase) and treated with interferon-alpha for 13 years, developed renal failure. Renal biopsy showed thrombotic thrombocytopenic purpura, but intensive therapy including plasma exchange and steroid administration was not effective. The activity of von Willebrand factor-cleaving protease was detectable at the intermediate level (15-46%) during the clinical course, suggesting that this case was not compatible with the previously reported pattern of idiopathic or drug-induced thrombotic thrombocytopenic purpura, but with the pattern associated with malignant disease or immunological disorders. Further studies to determine the effects of interferon-alpha on endothelial cells in chronic myelogenous leukemia patients are needed.
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PMID:Von Willebrand factor-cleaving protease activity remains at the intermediate level in thrombotic thrombocytopenic purpura. 1587 Apr 91

The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN-alpha. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN-alpha, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long-term IFN-alpha therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia.
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PMID:Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myeloid leukaemia. 1650 32

Imatinib mesylate (Gleevec, Glivec; Novartis, Basel, Switzerland) is a specific tyrosine kinase inhibitor that has become the gold-standard treatment for patients with chronic myeloid leukemia. Several tyrosine kinases inhibited by imatinib are expressed in the kidney, and although the drug is usually well tolerated, several cases of acute renal failure were reported. We describe for the first time a case of a patient treated by imatinib for chronic myeloid leukemia who developed partial Fanconi syndrome with mild renal failure, which leads to a discussion of the pathophysiological characteristics of imatinib-induced renal toxicity. Patients on long-term imatinib treatment should be monitored for renal failure, as well as proximal tubule dysfunction, including hypophosphatemia.
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PMID:Partial fanconi syndrome induced by imatinib therapy: a novel cause of urinary phosphate loss. 1821 7

Tyrosine kinase inhibitors (TKIs) directed against the Bcr-Abl kinase have revolutionized the treatment of chronic myelogenous leukemia (CML). Relatively little is known regarding the effects of these agents on the kidney. Clinically, there have been a handful of reports associating imatinib with acute renal failure. Preclinical reports indicate that imatinib inhibits signaling pathways which may play a role in renal injury. We report the case of a patient with imatinib-resistant CML who developed renal failure after being placed on dasatinib. When she later became resistant to dasatinib she was switched to nilotinib. Shortly thereafter, she became dialysis-independent. Second-generation Bcr-Abl TKIs may influence renal function based on differential inhibition of related tyrosine kinases.
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PMID:Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia. 1883 38

Imatinib mesylate (IM), nilotinib and dasatinib are tyrosine kinase inhibitors (TKIs) that have revolutionized the treatment of chronic myeloid leukemia (CML). Data regarding the effect of TKIs on the kidney or their safety in patients with renal failure is lacking. We describe a patient with CML who developed renal failure during IM treatment which resolved upon discontinuation of the drug and was not exacerbated by the administration of nilotinib. The literature reporting on the association between TKIs and renal failure is reviewed and the postulated mechanisms including tubular dysfunction caused by the drug or tumor lysis syndrome are discussed.
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PMID:Renal failure associated with tyrosine kinase inhibitors--case report and review of the literature. 1964 May 84

Imatinib mesylate (IM) is a very important drug in the treatment of gastrointestinal stromal tumors (GISTs) and chronic myeloid leukaemia (CML). In large clinical trials conducted until now it demonstrated a good cardiac safety profile. However during the last years many reports indicated a possible IM-induced cardiotoxicity. Here we report a case of a patient with a GIST who developed a severe and irreversible cardiac failure during IM treatment. Interestingly, she suffered from chronic renal failure, a condition that does not contraindicate treatment. Our opinion is that IM-induced cardiotoxicity could be facilitated by the presence of relevant comorbidities such as pre-existing cardiovascular disease or renal failure, commonly present in daily practice but excluded from clinical trials. Phase IV studies are needed to address the question of the real incidence of IM-induced cardiotoxicity in the general population.
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PMID:Congestive heart failure during imatinib mesylate treatment. 1965 83


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