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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The WHO classification published in 2001 defined a new category of hematological disease, myelodysplastic/myeloproliferative diseases (MDS/MPD), that have both myelodysplasia and myeloproliferation at the time of initial presentation. This category consists of four subclasses, chronic myelomonocytic leukemia (CMML), atypical CML(aCML), juvenile chronic myelogenous leukemia and MDS/MPD-unclassifiable (MDS/MPD-u). In order to clarify the clinical features of these diseases, we analyzed clinical data of tentatively diagnosed MDS/MPD cases in the past ten years accumulated from affiliated hospitals. By reviewing the data of each case according to the criteria, we diagnosed 31 cases of MDS/MPD, including 22 cases of CMML, 5 cases of aCML and 4 cases of MDS/MPD-u. Male predominance and high age were common among these three subclasses. The prognosis of CMML was poor compared to other subclasses because of the high incidence of blast crisis. It is noteworthy that blast crisis in CMML exclusively occurred within one year after diagnosis. Young age, a high percentage of blasts in the peripheral blood, splenomegaly, lymphadenopathy and clonal cytogenetic abnormality were associated with blast crisis. It is suggested that there are two subgroups in CMML which differ in disease progression. Thus, these indicators may be useful in deciding the therapeutic strategy including hematopoietic cell transplantation for the high risk subgroup. There were four MDS/MPD cases with a history of preceding hematological diseases, such as aplastic anemia, MDS or malignant lymphoma. Among these, three cases with a long-term history of treatment with metenolone acetate developed CMML. It is suggested that the long-term effect of androgen plays a role in the pathophysiology of CMML.
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PMID:[Clinical features of a new category, myelodysplastic/myeloproliferative diseases, defined by WHO classification]. 1663 72

Mutations in TERC, the RNA component of telomerase, result in autosomal dominant dyskeratosis congenita (DC), a rare bone marrow failure syndrome. TERC mutations have been detected in a subset of patients previously diagnosed with aplastic anemia and myelodysplastic syndrome (MDS), and these TERC mutations are clinically relevant as patients with DC respond poorly to conventional therapies. We aimed to determine the frequency of TERC mutations in pediatric patients with aplastic anemia and MDS who required a hematopoietic stem cell transplant. We obtained 284 blood samples from the National Donor Marrow Program Research Sample Repository from children and adolescents with bone marrow failure who underwent an unrelated stem cell transplant. We screened these samples for mutations in the TERC gene using direct DNA sequencing. We found 2 patients with sequence alterations in TERC. We identified a 2 base pair deletion (-240delCT) in a 4-year-old child with MDS and a single nucleotide alteration (-99-->CG) in a 1-year-old child with juvenile myelomonocytic leukemia. Screening for TERC gene mutations is unlikely to diagnose occult DC in children with severe bone marrow failure who require a hematopoietic stem cell transplant.
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PMID:Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome. 1682 92

Group of heterogeneous clonal hematopoietic disorders usually associated with other genetic disorders called for myelodysplastic syndromes (MDS) are occurring less common in children. The WHO classification based on French-American-British (FAB) MDS morphology is widely accepted in adults but does substantially differe from the one applicable in children. The differencies have recently been published. In our national retrospective study we analyzed 99 children with MDS and JMML diagnosed between 1989 and 2003 in Poland. Chemotherapy is generally, not useful in childhood MDS. With a few exceptions hematopoieitic stem cell transplantation (HSCT) is the only curative treatment for children with MDS. In this nationalexperience use of a relative or an unrelated donor results are almost comparable to the internationally published ones. Successful management of the disease needs to be run on a basis of cooperative efforts between clinicians and scientists involved in pediatric MDS. This includes need for centralized update and morphologic re-evaluation of all patients in the country as well as appointments on a regular basis for all individuals involved in treatment of MDS for quality control.
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PMID:[What to improve in approach to diagnose and treat pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia in Poland?]. 1689 96

Activating mutations of the PTPN11 gene encoding the SHP2 tyrosine phosphatase is the most common genetic abnormality in juvenile myelomonocytic leukemia and is sporadically observed in myelodysplasia (MDS) and acute myeloid leukemia (AML). An unselected series of 140 patients with therapy-related MDS or AML were investigated for mutations of PTPN11 in Exons 3, 4, 8, and 13. Four cases had mutations of the gene; three of these had deletions or loss of chromosome arm 7q. Two cases had rare balanced translocations to chromosome band 21q22 with rearrangement of the RUNX1 gene and the other two patients had rare balanced translocations to chromosome band 3q26 with rearrangement of the EVI1 gene. The findings support cooperation between so called Class I and Class II mutations in leukemogenesis.
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PMID:Mutations of the PTPN11 gene in therapy-related MDS and AML with rare balanced chromosome translocations. 1733 Feb 62

Splenectomy has been performed as a palliative treatment both in adults and children with myelodysplastic syndrome (MDS). However, there is no report describing the course after splenectomy in children with MDS. The aim of this study was to evaluate the impact of splenectomy on the outcome of six children with juvenile myelomonocytic leukemia (JMML) who had no HLA identical donor and who became unresponsive to chemotherapy. Persistent thrombocytopenia, increased erythrocyte transfusion requirement and massive splenomegaly were the indications for splenectomy. Hemoglobin values and platelet counts improved following splenectomy in five out of the six patients. Erythrocyte transfusion requirements decreased and none of the patients who responded received erythrocyte transfusion for at least six months. More importantly, the quality of life improved markedly. No mortality related to splenectomy was observed. In conclusion, splenectomy may be considered as a safe supportive treatment approach for some children with JMML.
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PMID:The role of splenectomy in children with juvenile myelomonocytic leukemia. 1790 14

Myeloid malignancies in children include de novo acute/chronic myeloid leukemia (AML/CML) and secondary malignancy due to genetic predisposition or previous therapy. Generations of clinical trials for childhood myeloid disorders have resulted in improved disease characterization and outcome, and defined therapeutic strategies combining chemotherapy, biologic response modifiers and immunotherapy. With advancement in molecular genetics and the development of sensitive techniques to detect response, residual disease and relapse, therapy can be tailored in a risk-based manner using clinical and biological/molecular parameters and several 'good-risk' myeloid malignancies enjoy high cure rates with targeted therapy. However, hematopoietic stem cell transplant remains the best method of treatment intensification for poor-risk disorders such as relapsed/secondary AML, myelodysplastic syndrome and juvenile myelomonocytic leukemia. Indications for transplant and outcomes of previous clinical studies, and novel transplant strategies designed to improve safety and efficacy of the procedure are reviewed.
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PMID:Hematopoietic stem cell transplantation for childhood malignancies of myeloid origin. 1817 16

The 2001 World Health Organization (WHO)-sponsored classification of hematopoietic tumors has, for the first time, clearly defined a group of rare myeloid neoplasms termed myelodysplastic/myeloproliferative diseases (MDS/MPDs). This group includes three main entities, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia, and also several less well defined, 'unclassifiable' disorders with MDS/MPN-like features. In the upcoming fourth edition of the WHO fascicle, due out later this year, the term 'MPD' is replaced by 'myeloproliferative neoplasm (MPN)'. Accordingly, the term MDS/MPD is being replaced by 'MDS/MPN' that will be used in this review. Although much progress has been made in understanding the molecular pathogenesis of myeloid neoplasms, most of the diseases included in the group of MDS/MPN still remain 'clinicopathologically assigned'. In other words, they can only be accurately categorized by a careful multiparametric approach that is based on the integration of bone marrow and peripheral blood morphology with other laboratory and clinical findings. The current 'spotlight' review provides practical guidelines, which should allow for a reproducible classification of these uncommon neoplasms when encountered in clinical practice.
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PMID:The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. 1848 Aug 33

In 1982, chronic myelomonocytic leukemia (CMML) was first classified in the category of myelodysplastic syndromes (MDSs), but it always seemed somewhat out of place compared with the rest of the MDS categories. In the 1990s, many argued that there were two different forms of CMML, a proliferative type and a myelodysplastic type. Then in 2001 the World Health Organization created a new category called the mixed myelodysplastic/myeloproliferative diseases, under which CMML was included. Although we still do not understand much about CMML pathogenesis nor do we have specific therapies for this disease, at least now most agree that it is in an appropriate category such that other areas of investigation can now proceed. On the other hand, we now understand a great deal of the pathogenesis underlying the disease now called juvenile myelomonocytic leukemia (JMML). JMML also fits in the new category of mixed myelodysplastic/myeloproliferative diseases. JMML is an excellent model malignancy for investigating and understanding dysregulated and aberrant signal transduction in the Ras pathway. It has also served as a teaching tool for exploring inherited predispositions to cancer.
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PMID:Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. 1854 91

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive, clonal hematopoietic disorder of childhood with features of both myelodysplasia (thrombocytopenia, anemia) and myeloproliferation (leukocytosis, monocytosis). In most cases there is marrow hypercellularity, splenomegaly, and extramedullary involvement. In 1997 an international consensus on terminology was reached and guidelines/criteria for diagnosis were proposed. A recent World Health Organization classification described the current diagnostic criteria of JMML. Although the diagnosis of JMML has been facilitated, it can be challenging, especially in the early stages or when it 1st presents as an extramedullary tumor. We report a series of 7 cases diagnosed over a period of 10 years (from January 1, 1996, to December 31, 2005). Two cases had interesting associated findings that would potentially lead to delay in diagnosis or misdiagnosis. Two other cases had extramedullary involvement with symptoms referable to the organs of involvement at presentation. Clinical and pathologic findings are summarized with a review of relevant literature.
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PMID:Juvenile myelomonocytic leukemia: report of seven cases and review of literature. 1872 Oct 5

Germline mutations in PTPN11 gene cause Noonan syndrome and the clinically similar LEOPARD syndrome (LS). LS is a rare congenital developmental disorder characterized by multiple lentigines, cardiac abnormalities, facial dysmorphism, retardation of growth, and deafness. Mutations in exons 7 and 12 of the PTPN11 gene can be identified in nearly 90% of patients with LS. PTPN11 gene encodes for an ubiquitously expressed protein tyrosine phosphatase SHP-2 involved in a variety of intracellular signaling processes in development and hematopoiesis. Somatic PTPN11 mutations contribute to leukemogenesis in children with hematologic malignancies including juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplasia. Two cases of leukemia (acute myeloid leukemia) have been reported in children with LS. The authors describe for the first time a girl with genetically confirmed LEOPARD syndrome presenting with common acute lymphoblastic leukemia.
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PMID:Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome. 1879 37


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