Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.
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PMID:Somatic mutations in the neurofibromatosis 1 gene in human tumors. 156 47

Eleven children underwent BMT for therapy-related MDS or leukemia, four from HLA-identical siblings and seven from unrelated donors. Ten of the 11 were conditioned with busulfan and cyclophosphamide as the majority had received prior irradiation to the chest and/or abdomen. All patients engrafted. Regimen-related toxicity was more common when compared to historical controls. Eight patients developed acute GVHD and four of eight who survived 100 days post transplant developed extensive chronic GVHD. Non-relapse related mortality occurred in three patients. Five patients developed recurrent malignancy: one died from recurrence of osteosarcoma, three died of recurrent leukemia or MDS and another developed two subsequent malignancies (duodenal carcinoma and anaplastic astrocytoma). Three survive disease-free at 14+, 22+ and 43+ months for a 2 year actuarial cancer-free survival of 24% (95% confidence interval = 5-53%). Although allogeneic BMT can be curative, regimen-related toxicity is frequent and recurrent malignancy remains the major obstacle.
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PMID:Bone marrow transplantation in pediatric patients with therapy-related myelodysplasia and leukemia. 1003 46

A 3-month-old boy and a 29-year-old woman presented with myelodysplastic syndrome (MDS) following therapy for primary malignant brain tumor. Both received intensive alkylating agent doses for induction and maintenance chemotherapy combined with craniospinal or cranial radiation for medulloblastoma and anaplastic astrocytoma, respectively. They developed refractory anemia and pancytopenia. Approximately 9 years after the completion of induction chemoradiotherapy, chromosomal analysis of bone marrow cells resulted in the diagnosis of MDS. The boy died of leukemic evolution 15 months later, the woman died of hematopoietic failure 3 months later. The most common symptom of MDS is refractory anemia, either alone or as part of bi- or pancytopenia. Clonal proliferation with chromosomal analysis of bone marrow cells establishes the diagnosis of MDS. Patients with malignant brain tumors are at risk of the development of MDS as a late complication of chemotherapy based on high cumulative doses of alkylating agents.
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PMID:Myelodysplastic syndrome following therapy for brain tumor--two case reports. 1201 70

In patients with recurrent malignant glioma, treatment-related myelodysplastic syndrome (t-MDS) and acute leukemia are rare adverse effects because the median survival after relapse is limited. We report a 44-year-old woman with t-MDS (refractory anemia with excess blasts) following treatment of recurrent anaplastic astrocytoma with temozolomide (TMZ). A cytogenetic study showed del (3)(q11.1). MDS was diagnosed 8.4 months after beginning TMZ. The disease rapidly evolved into acute leukemia within 1 month after the onset of MDS, and the patient died 1 month later during induction chemotherapy. The prognosis of t-MDS is generally poor. Considering the increasing use of TMZ, which is regarded as a drug with moderate toxicity, careful follow-up with routine blood testing is vital.
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PMID:Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma. 1573 23

Therapy-related myelodysplastic syndrome and acute leukemia after treatment with temozolomide have rarely been described in the literature. Only 10 cases in association with temozolomide have been documented. The cases included anaplastic astrocytoma (4 cases), anaplastic oligodendroglioma (2 cases), low grade astrocytoma (2 cases), low grade oligodendroglioma (1 case), and one case of secondary Philadelphia-positive acute lymphoblastic leukemia in a patient with glioblastoma multiforme. Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia associated with der(1;7)(q10;p10) in a glioblastoma multiforme patient treated with temozolomide. Results of bone marrow morphology, chromosome, and fluorescent in situ hybridization (FISH) analyses, as well as the clinical history, strongly suggest a treatment-related etiology in our case. In past reports, karyotypes in cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia mostly demonstrated abnormalities in chromosomes 5 and 7. However, we report a case of temozolomide-related myelodysplastic syndrome/acute myeloid leukemia with der(1;7)(q10;p10), possibly the first reported case, to the authors' knowledge.
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PMID:Therapy-related myelodysplastic syndrome/acute myeloid leukemia after treatment with temozolomide in a patient with glioblastoma multiforme. 1988 Jul 68

Temozolomide (TMZ) is a second-generation oral alkylating agent that functions against a number of central nervous system neoplasms, and is generally used to treat high-grade gliomas, including anaplastic astrocytoma and glioblastoma multiforme. Therapy-related secondary myelodysplastic syndrome and acute myeloid leukemia have been reported in patients following prolonged exposure to TMZ. However, TMZ-related acute lymphoblastic leukemia (ALL) is extremely rare. The present study describes the case of an 11-year-old boy with a 3-day history of generalized tonic-clonic seizures and a contrast-enhanced lesion in the left temporooccipital region with focal cystic degeneration, as detected by magnetic resonance imaging. The patient underwent craniotomy and gross-total resection andpathological analysis confirmed the diagnosis of giant cell glioblastoma. Postoperatively, the patient received TMZ-based concurrent chemoradiation during radiotherapy, and developed B-cell ALL 6 months following TMZ treatment. A thorough literature search identified only six published cases of TMZ-related ALL. The chemotherapeutic efficacy of TMZ has been identified, however, its leukemogenic potential should be emphasized among practitioners and patients. Further studies are required to determine the specific pathogenic mechanism of TMZ-related ALL. Close hematological monitoring of patients following TMZ treatment is vital and a high index of suspicion is necessary.
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PMID:Acute lymphoblastic leukemia following temozolomide treatment in a patient with glioblastoma: A case report and review of the literature. 2980 3