Pathogenetic implications of internuclear bridging in myelodysplastic syndrome. An eastern cooperative oncology group/southwest oncology group cooperative study

Head, David R.; Kopecky, Kenneth J.; Bennett, John M.; Grenier, Kathy; Morrison, Francis S.; Miller, Kenneth B.; Grever, Michael R.

doi:10.1002/1097-0142(19891201)64:11<2199::aid-cncr2820641102>3.0.co;2-3

Cited by 15 publications

(4 citation statements)

References 14 publications

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“…It must be emphasized that by LM we did not find INB in 21% of our patients with molecular proven CDAI, although they are considered as the most specific LM morphological hallmark of the disease . However, their specificity has been questioned as they also may appear as an unspecified dyserythropoietic finding in acute myeloid leukemia, in myelodysplastic syndrome before leukemic transformation, in megaloblastic anemia, and in the presence of unstable hemoglobin . Although we did not count the morphological LM findings found in each sample, Heimpel et al found those to be infrequent, for example, INB found in 3% of erythroblasts (range 1.4‐7.9) …”

Section: Discussionmentioning

confidence: 99%

Morphological features of congenital dyserythropoietic anemia type I: The role of electron microscopy in diagnosis

Resnitzky

Shaft

Shalev

et al. 2017

European J of Haematology

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Section: Discussionmentioning

confidence: 99%

Morphological features of congenital dyserythropoietic anemia type I: The role of electron microscopy in diagnosis

Resnitzky

Shaft

Shalev

et al. 2017

European J of Haematology

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“…In addition to chromosomal instability noted by many FA investigators, we have noted internuclear bridging peculiar to FA mutant cells. Internuclear bridging is a phenomenon seen in cells displaying genomic instability (51,52). Cells with abnormal chromosomal segregation and chromosomal structures such as those in FA can form internuclear bridging, presumably because of lagging chromosomes (53).…”

Section: Fig 2 Fancg Is Phosphorylated In Vivomentioning

confidence: 99%

Phosphorylation of Fanconi Anemia (FA) Complementation Group G Protein, FANCG, at Serine 7 Is Important for Function of the FA Pathway

Qiao¹,

Mi²,

Wilson

et al. 2004

Journal of Biological Chemistry

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Fanconi anemia (FA) 1 is a genetic disease of cancer susceptibility marked by congenital defects, bone marrow failure, and myeloid leukemia (1-4). To date at least 11 complementation groups have been defined (5-7). Eight genes have been cloned (8 -17). However, the gene products resemble no known proteins and have few identifiable functional protein motifs. One exception is the recently cloned FANCL gene, which contains the ubiquitin ligase motif. In addition, the FANCD1 gene has been identified as BRCA2, one of the familial breast cancer genes.Cells derived from patients with the FA exhibit characteristic hypersensitivity caused by DNA cross-linking agents and generalized decreased survival (18 -22). However, no defined biochemical mechanism for this hypersensitivity has been elucidated, although studies have implicated cytokine dysregulation, excessive, oxidative damage, defects in DNA repair, and lack of cell cycle control (23-27). Patient and cellular phenotypes across all the complementation groups are similar, suggesting an inter-relatedness or cooperativity between the FA proteins.This cooperativity has been borne out by work we have done in showing binding of FANCA and FANCC in a protein complex in both nucleus and cytoplasm (28 -30). Recent work has found the FANCE, FANCF, FANCG, and FANCL proteins in the complex as well (31-34). A large complex is suggested by our recent work (35), and binding does not occur in any of the complementation groups except the FA-D1, D2, I, and J groups (7).One clue to FA function lies in the study of the FANCA protein, which contains a classic bipartite nuclear localization signal and is phosphorylated. Generally, FANCA nuclear localization, phosphorylation, and binding to FANCC are abolished in all complementation groups except the FA-D1 and D2 groups (28 -30, 33). This suggests that a nuclear event is critical to the normal function of the FA proteins, and the aberrant proteins in the FA-D groups may have a role downstream of the FA complex in the nucleus. However, some have found FANCA point mutants that are expressed, translocated to the nucleus, and are phosphorylated to some extent. Some of these mutants are of intermediate MMC sensitivity (36).Over the years, little information has been found that addresses the regulation of the FA proteins. mRNA or protein levels change little in response to DNA damage or the cell cycle. Our recent work has revealed that at least a subset of the FA proteins resides in the nucleus bound to chromatin, where increased protein binding occurs in response to DNA damage (37). One of the non-core complex FA proteins, FANCD2, becomes monoubiquitinated in response to DNA damage (38).In addition, we have shown during the cell cycle that the FA proteins detach from chromatin during mitosis, and FANCG becomes phosphorylated while remaining part of the complex (37). One group has demonstrated that FANCG has a isoform seen in asynchronous cells that is phosphatase sensitive (39).In this paper we report the identification of a phosphopeptide from ...

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“…Furthermore, although internuclear chromatin bridges which connect partially separated erythroblasts are characteristic of CDA type I, they are also encountered in acquired dyserythropoiesis, for example in some patients with the acquired myelodysplastic syndrome (Bethlenfalvay et al, 1986;Head et al, 1989).…”

Section: General Characteristics Of Congenital Dyserythropoietic Anaementioning

confidence: 99%

Dyserythropoiesis and Congenital Dyserythropoietic Anaemias

Wickramasinghe

1997

Br J Haematol

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Pathogenetic implications of internuclear bridging in myelodysplastic syndrome. An eastern cooperative oncology group/southwest oncology group cooperative study

Cited by 15 publications

References 14 publications

Morphological features of congenital dyserythropoietic anemia type I: The role of electron microscopy in diagnosis

Morphological features of congenital dyserythropoietic anemia type I: The role of electron microscopy in diagnosis

Phosphorylation of Fanconi Anemia (FA) Complementation Group G Protein, FANCG, at Serine 7 Is Important for Function of the FA Pathway

Dyserythropoiesis and Congenital Dyserythropoietic Anaemias

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