Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shwachman's syndrome is a rare congenital disorder associated with neutropenia and exocrine pancreatic insufficiency. We describe the development of acute myeloid leukemia in a 38-year-old patient with Shwachman's syndrome following three years of pancytopenia. After chemotherapy the leukemic clone was eradicated, however, the patient's bone-marrow hypoplasia persisted beyond 180 days with neutropenia that responded to administration of granulocyte colony-stimulating factor. Despite the patient's low erythropoietin levels, administration of erythropoietin did not improve his hemoglobin. We review previously reported cases of leukemia complicating Shwachman's syndrome with emphasis on the persistent risk of complications in patients with congenital bone-marrow failure syndromes.
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PMID:Acute leukemia complicating bone marrow hypoplasia in an adult with Shwachman's syndrome. 751 52

Clinical evidence for a link between aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and hypoplastic leukaemia is provided by studies of clonal disorders, which may be a complication of congenital or acquired aplastic anaemia. Fanconi's anaemia is the most common congenital disorder and leukaemia occurs in at least 10% of cases. In acquired aplastic anaemia, a high incidence of myelodysplastic syndrome (MDS) was noted in patients with aplastic anaemia, seemingly cured of their aplasia by antilymphocyte globulins (ALG). In a recent survey, the 10-year cumulative incidence rates were 9.6% for MDS, 6.6% for acute leukaemia (115-fold higher than in the general population). Biological evidence is provided by bone marrow morphology, as a certain degree of dysmyelopoiesis is not unusual in aplastic anaemia. Cytogenetic analyses in aplastic anaemia are scarce, but data have shown clonal cytogenetic abnormalities at diagnosis in otherwise typical aplastic anaemia. Recently, flow cytometry to assess the glycosyl-phosphatidylinositol (GPI) molecule defect in PNH has demonstrated that a significant proportion of patients with otherwise typical aplastic anaemia have, in fact, a GPI defect due to alterations within the PIG-A gene. Finally, aplastic anaemia patients were recently reported to have molecular evidence of clonal haematopoiesis; this must now be discussed in light of recent clonality studies in normal individuals. The clinical and biological evidence for a link between aplastic anaemia, PNH and hypoplastic leukaemia allows the generation of a model of aplastic anaemia as a possible pre-pre-leukaemic disorder.
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PMID:Could aplastic anaemia be considered a pre-pre-leukaemic disorder? 898 43

Poland's syndrome, a rare congenital disorder with pectoralis muscular girdle defect, have been reported in association with lymphoreticular malignancies in the past. Childhood solid tumors in association with this congenital anomaly have not been reported so far. We describe this rare association of Poland's syndrome and Wilms tumor. Due to the possibility of increased risk of leukemogenesis in patients with Poland's syndrome, chemo-radiation therapy of Wilms tumor in our patient may increase the risk of secondary leukemia. Therapeutic modification of primary cancer in these patients may be necessary with careful long-term follow-up for early detection and treatment of secondary cancer.
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PMID:Poland's syndrome and Wilms tumor: an unusual association. 937 93

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder featuring exocrine pancreatic insufficiency, growth retardation, and bone marrow dysfunction. Reports suggest that nearly 25% of all cases are complicated with leukemia. Although stem cell transplantation is the sole option for these patients, successful results are rarely obtained. Poor outcomes are often related to graft failure and cardiac and other organ toxicities. We describe in this report successful unrelated donor bone marrow transplantation for a patient with SDS who progressed to acute myelogenous leukemia. The patient received attenuated intensified chemotherapy because of his intolerance to ordinary chemotherapy and went into remission. Sustained unrelated donor bone marrow engraftment was accomplished after treatment with a reduced amount of cyclophosphamide and antithymocyte globulin with 12 Gy of total body irradiation as a conditioning regimen. To the best of our knowledge, this report is the first to describe unrelated donor bone marrow transplantation with complete engraftment for an SDS patient with myelogenous leukemia.
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PMID:Successful unrelated donor bone marrow transplantation for Shwachman-Diamond syndrome with leukemia. 1500 50

Down syndrome is a common congenital disorder affecting approximately 1/1000 live births. Newborns and children with Down syndrome may present with many haematological problems. In addition, benign abnormalities of the blood count and blood film, which may manifest at any age, population-based and cancer-based registries and clinical trials suggest there is a approximately 12-fold increased risk of acute lymphoblastic leukaemia in the age group of 5-30 years that rises to approximately 40-fold in children younger than 5 years, and that there is a approximately 150-fold increased risk of acute myeloid leukaemia in children younger than 5 years. There is also a virtually unique predisposition to a transient neonatal leukaemia, known as transient abnormal myelopoiesis. Deaths from leukaemia, in part, account for the excess mortality associated with Down syndrome. This article reviews the clinical presentation and the progress made in the management of these disorders over the past decade. It also briefly considers the recent exciting scientific advances that have potential to transform management of leukaemia in children with Down syndrome and also have implications for management of childhood leukaemia more generally.
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PMID:Haematology of Down syndrome. 1780 20

Mutations in BCOR (Bcl6 corepressor) are found in patients with oculo-facio-cardio-dental (OFCD) syndrome, a congenital disorder affecting visual system development, and loss-of-function studies in zebrafish and Xenopus demonstrate a role for Bcor during normal optic cup development in preventing colobomata. The mechanism whereby BCOR functions during eye development to prevent colobomata is not known, but in other contexts it serves as a transcriptional corepressor that potentiates transcriptional repression by B cell leukemia/lymphoma 6 (BCL6). Here, we have explored the function of the zebrafish ortholog of Bcl6, Bcl6a, during eye development, and our results demonstrate that Bcl6a, like Bcor, is required to prevent colobomata during optic cup formation. Our data demonstrate that Bcl6a acts downstream of Vax1 and Vax2, known regulators of ventral optic cup formation and choroid fissure closure, and that bcl6a is a direct target of Vax2. Together, this regulatory network functions to repress p53 expression and thereby suppress apoptosis in the developing optic cup. Furthermore, our data demonstrate that Bcl6a functions cooperatively with Bcor, Rnf2 and Hdac1 in a common gene regulatory network that acts to repress p53 and prevent colobomata. Together, these data support a model in which p53-dependent apoptosis needs to be tightly regulated for normal optic cup formation and that Bcl6a, Bcor, Rnf2 and Hdac1 activities mediate this regulation.
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PMID:Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata. 2366 49

Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple central cartilaginous tumors (enchondromas) in association with cutaneous spindle cell hemangiomas. These patients have a high incidence of malignant transformation. No familial case is known and the etiopathogenic cause remains unknown. In enchondromatosis (Ollier disease, OD), which is comprised of enchondromas only, 4 mutations in the PTHR1 gene have been identified in 4 patients; 3 were somatic and 1 was germline. No PTHR1 mutations have been detected in MS, whereas somatic IDH1 and, more rarely, IDH2 mutations have been observed in 77% of patients with MS and 81% of patients with OD. These genetic alterations are shared with other tumors, including glioma, leukemia and carcinoma. To search for underlying somatic genomic causes, we screened MS tissues using Affymetrix SNP-chips. We looked for CNVs, LOH and uniparental isodisomy (UPID) by performing pairwise analyses between allelic intensities in tumoral DNA versus the corresponding blood-extracted DNA. While common chromosomal anomalies were absent in constitutional DNA, several shared CNVs were identified in MS-associated tumors. The most frequently encountered somatic alterations were localized in 2p22.3, 2q24.3 and 14q11.2, implicating these chromosomal rearrangements in the formation of enchondromas and spindle cell hemangiomas in MS. In one chondrosarcoma specimen, large amplifications and/or deletions were observed in chromosomes 3, 6, 9, 10, 12, 13, and 19. Some of these genetic changes have been reported in other chondrosarcomas suggesting an etiopathogenic role. No LOH/UPID was observed in any Maffucci tissue. Our findings identify frequent somatic chromosomal rearrangements on 2p22.3, 2q24.3 and 14q11.2, which may unmask mutations leading to the lesions pathognomonic of MS.
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PMID:Common somatic alterations identified in maffucci syndrome by molecular karyotyping. 2556 25

Chediak-Higashi syndrome (CHS) is an uncommon and fatal congenital disorder. The characteristic features of CHS are partial oculocutaneous albinism, increased vulnerability to infections, presence of abnormal large granules in leukocytes and an accelerated lymphohistiocytic phase. Accelerated phase at initial presentation is rarely seen as it is usually preceded by repeated episodes of infections. Hence this interesting case of a four-month-old Indian child born to consanguineous parents in accelerated phase at initial presentation is described. The boy presented with fever, hepatosplenomegaly, and cleft lip. Clinical diagnosis was leukemia or a lysosomal storage disorder. Cytopaenias, lymphohistiocytic infiltration in bone marrow, and the characteristic large granules in leucocytes helped in the diagnosis, emphasizing the importance of bone marrow in diagnosis of unusual presentation of this rare disorder.
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PMID:Accelerated Phase of Chediak-Higashi Syndrome at Initial Presentation: A Case Report of an Uncommon Occurrence in a Rare Disorder. 2681 3

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia. Of the three cases of AML found in TAR patient, only one was reported in an adult. We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.
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PMID:Acute myeloid leukemia in a patient with thrombocytopenia with absent radii: A case report and review of the literature. 2825 46