Clonal chromosomal abnormalities in Fanconi's anaemia: what do they really mean?

Alter, Blanche P.; Scalise, Angela; McCombs, J. L.; Najfeld, Vesna

doi:10.1111/j.1365-2141.1993.tb03362.x

Cited by 37 publications

(4 citation statements)

References 15 publications

(8 reference statements)

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“…[ 34 36 ] Such a delay in identification of FA patients and at-risk families can be avoided by performing the MMC-stress test in patients with macrocytosis and decreased platelet count, as observed during screening of complete blood count with differentials. [ 34 37 ] In a recent report, it is shown that MMC-induced DNA damage also can be used as an index for FA identification. [ 38 ] We suspect a correlation between sensitivity of cells to alkylating agents, measured as breakage index, and the amount of cells containing aberrations, measured as the percentage of aberrant cells.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

2011

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BACKGROUND:Fanconi anemia (FA) is a rare autosomal recessive genetic disorder that shows an increased sensitivity to the intercalating agents such as mytomycin C (MMC), measured as chromosomal aberrations. This study was conducted to differentiate between FA and “idiopathic” aplastic anemia on the basis of induced chromosomal breakage study with MMC.MATERIALS AND METHODS:MMC stress tests in different final concentrations of 20 and 50 ng/ml of MMC were conducted on peripheral blood lymphocytes from 32 patients with aplastic anemia and 13 healthy controls. Fifty nanograms per milliliter of MMC from old, fresh and frozen stocks was used to check the sensitivity of diagnosis on FA-diagnosed patients. Statistical analysis was used for the assessment of aberrations, including chromatid and chromosome breaks and exchanges.RESULTS:Eight patients (25%) with a very high percentage of chromosomal breakage were diagnosed as FA on the basis of the chromosomal breakage study. Six of these patients exhibited congenital anomalies at presentation, while another two lacked such anomalies or had minor physical problems. Freshly made MMC has shown more sensitivity to detect FA patients compared with frozen or 1-week-old MMC stock.CONCLUSIONS:The study indicates that freshly made MMC stress test provides an unequivocal means of differentiation between FA and “idiopathic” aplastic anemia. Further, the study, the first of its kind from Iran, stresses on the need for conducting this test in all aplastic anemia cases, even those without congenital anomalies, for accurate and timely diagnosis of FA to implement appropriate therapy.

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Section: Discussionmentioning

confidence: 99%

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

2011

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“…12–14 However, incomplete characterization of the aberrations owing to limitations in available techniques, the absence of the more common recurring abnormalities in AML, the presence of background chromosomal instability generating nonclonal abnormalities, and the occasional report of “transient” clones have raised the issue of the clinical significance of these clonal abnormalities. 14,15 More recently, Tonnies et al 16 have shown that a clone resulting in an extra copy of the distal long arm of chromosome 3 in FA is associated with a poor prognosis. Yet questions remain regarding the spectrum and clinical significance of clonal cytogenetic abnormalities.…”

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confidence: 99%

Diagnosis of Myelodysplastic Syndrome Among a Cohort of 119 Patients With Fanconi Anemia

et al. 2010

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Predisposition to myelodysplastic syndrome (MDS) and acute leukemia is a hallmark of Fanconi anemia (FA). Morphologic criteria for MDS in FA are not well established, nor is the significance of clonal chromosomal abnormalities. We reviewed bone marrow samples of 119 FA patients: 23 had MDS, with the most common subtype refractory cytopenia with multilineage dysplasia. The presence of MDS was highly correlated with the presence of clonal abnormalities. Neutrophil dysplasia and increased blasts were always associated with the presence of a clone, in contrast with dyserythropoiesis. The most frequent clones had gains of 1q and 3q and/or loss of 7. Karyotype complexity also correlated with MDS. One third of patients with 3q as a sole abnormality had no MDS; patients with 3q and an additional abnormality all had MDS. The data provide a rationale for integrating cytogenetic findings with independently evaluated morphologic findings for monitoring bone marrow status in FA.

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“…Therefore, minimal diagnostic criteria for secondary MDS following an underlying IBMFS have been developed [33] (increased BM blast count, development of a hypercellular marrow in the presence of persistent PB cytopenias and acquired clonal chromosomal abnormalities). However, studies in FA and SDS indicate that clonal cytogenetic abnormalities are not universally associated with disease progression and poor outcomes since cytogenetic changes may persist for years without evolution to MDS/ AML [3,4,51].…”

Section: Secondary Mdsmentioning

confidence: 99%

Pediatric myelodysplastic syndromes

Hofmann

2015

J Hematopathol

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Pediatric myelodysplastic syndromes (MDS) are a group of rare clonal hematopoietic stem cell disorders characterized by varying degree of cytopenias, ineffective and dysplastic hematopoiesis, and the risk of leukemic transformation. The clinical, laboratory, and histologic presentation of pediatric MDS shares significant overlap with other inherited and acquired bone marrow failure (BMF) disorders. Given that the majority of pediatric patients with MDS present with a hypocellular bone marrow, the histopathologic diagnosis is challenging and usually requires ancillary molecular studies. While rapid advancements have been made in the field of adult MDS, the underlying genetics and pathophysiology of pediatric MDS are still poorly understood. The recent discovery of germline mutations in GATA2 leading to MDS suggests that some pediatric and young adult patients with MDS have an underlying genetic predisposition. Nevertheless, the molecular underpinnings remain poorly understood in most cases. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. Optimal timing of HSCT is not often straightforward, as some pediatric patients with lowgrade MDS have an indolent disease course while others show rapid progression to advanced MDS and leukemia. Lastly, the classification of pediatric MDS has evolved over the years and is different from the terminology currently used in adult MDS. This review will focus on the current classification schemes of pediatric MDS and address clinical, laboratory, and pathologic features, as well as diagnostic criteria, genomic advances, and therapeutic options and prognosis. Keywords Myelodysplastic syndromes. Refractory cytopenia of childhood (RCC). Refractory anemia with excess blasts (RAEB). Bone marrow failure. GATA2 haploinsufficiency. Histopathology

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Clonal chromosomal abnormalities in Fanconi's anaemia: what do they really mean?

Cited by 37 publications

References 15 publications

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

Diagnosis of Myelodysplastic Syndrome Among a Cohort of 119 Patients With Fanconi Anemia

Pediatric myelodysplastic syndromes

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