Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

Göhring, Gudrun; Giagounidis, Aristoteles; Büsche, Guntram; Hofmann, Winfried; Kreipe, Hans; Fenaux, Pierre; Hellström‐Lindberg, Eva; Schlegelberger, Brigitte

doi:10.3324/haematol.2010.026658

Cited by 17 publications

(19 citation statements)

References 20 publications

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“…Controversy exists regarding whether iFISH is necessary at the initial diagnosis of MDS and/or during followup. [4][5][6][7][8][9][10][11] Some studies suggest that iFISH can be performed only in cases of mitotic failure or abnormal karyotype. 5,7,8,11,12 Others have reported discrepancies between iFISH and Gbanding in MDS with monosomy 7 and observed that FISH can more sensitively reflect disease progression.…”

mentioning

confidence: 99%

Monitoring of the Clonal Fraction by Fluorescence In Situ Hybridization in Myelodysplastic Syndrome: Comparison With International Working Group Treatment Response Criteria

Park

Kim²,

Kong³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-At the initial diagnosis of myelodysplastic syndrome (MDS) and/or during follow-up, the evaluation of chromosomal abnormalities is based on standard Gbanding, whereas the utility of fluorescence in situ hybridization (FISH) is still debated.Objectives.-To investigate whether interphase fluorescence in situ hybridization (iFISH) clone size at initial diagnosis of MDS is correlated with survival and whether changes in clonal fraction by iFISH are concordant with the MDS International Working Group response criteria during follow-up.Design.-A tailored FISH panel (À5/5qÀ, À7/7qÀ, þ8, À20/20qÀ, and þ1/1qþ), based on reported cytogenetic changes in Korean patients with MDS, was performed in 81 patients with MDS at initial diagnosis and in 28 patients during follow-up.Results.-During follow-up, absolute increases in the clone size by iFISH by 20% or more, with relative increases of 50% or more, compared with previous specimens, were associated with transformation to acute myeloid leukemia (P ¼ .001 and P ¼ .002, respectively). Of the 28 patients with abnormal iFISH results, 7 (25%) showed discordance between iFISH and MDS International Working Group responses. Concordance between clone size by G-banding and iFISH was higher in the refractory cytopenia with unilineage dysplasia/refractory cytopenia with multilineage dysplasia group during follow-up, whereas the group with refractory anemia with excess blasts showed higher correlation at initial diagnosis.Conclusions.-We conclude that iFISH can provide additional prognostic information and can predict the response to therapy in MDS.

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confidence: 99%

Monitoring of the Clonal Fraction by Fluorescence In Situ Hybridization in Myelodysplastic Syndrome: Comparison With International Working Group Treatment Response Criteria

Park

Kim²,

Kong³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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“…Aberrations in cell cycle control may promote accumulation of additional mutations and influence clonal progression to AML (26). In patients with MDSs, CDC25C is part of the commonly deleted region on chromosome 5q (27,28). Furthermore, alternative splicing of CDC25C has been observed in bone marrow samples from patients with MDS (29) and downstream of the SRSF2-P95 mutant (30).…”

Section: Discussionmentioning

confidence: 99%

Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in FLT3-ITD-positive AML

Perner

Schnöder

Fischer

et al. 2016

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Abstract. Background/Aim: The presence of FLT3-Internal tandem duplications (ITDs) in human acute myeloid leukemia (AML) is associated with a dismal prognosis. Altered cell-cycle activity has been reported in FLT3-ITD-positive AML; however, the mechanisms by which this oncogene influences cell-cycle activity remained so far elusive. Materials and MethodsAcute myeloid leukemia (AML) is a genetically heterogeneous disease characterized by clonal selection and accumulation of mutations during disease progression (1). FLT3 is one of the most frequently mutated genes in adult AML (2-4) that encodes for a receptor tyrosine kinase required for maintenance of normal hematopoiesis (5). During leukemia development, the occurrence of FLT3-internal tandem duplications (ITD) induces constitutive activation of the encoded receptor tyrosine kinase and leads to activation of downstream effectors, such as STAT5, ERK and AKT. Depending on cooperating oncogenic events, presence of FLT3-ITD may be associated with a poor prognosis in patients with AML (2, 6, 7). Recent reports also suggested that constitutive activation of FLT3-signaling might result in aberrant cell-cycle activity (8).Stringent regulation of cell-cycle activity is of major importance to ensure proper development of hematopoiesis and to orchestrate tissue regeneration. Conversely, deregulation of cell cycle-relevant proteins can promote the development of cancer (9, 10). The final steps during cell-cycle transition are controlled by cyclin-dependent kinases (CDKs) in complex with the appropriate cyclins. CDKs are preserved in an inactive state through phosphorylation of distinct amino acid residues. Several amino acid residues need to be dephosphorylated by cell division cycle 25 (CDC25) phosphatases (9, 10) to activate CDKs. Therefore, CDC25 phosphatases are essential regulators of cell cycle progression in malignant and non-malignant cells. In mammals, this group of phosphatases consists of three homologues, CDC25A, CDC25B and CDC25C. These are involved in pathogenesis of human malignancies (9, 10) and, specifically, myeloid leukemia (11, 12). While CDC25A is important for S-phase entry and, crucial for regulating cellular proliferation (13), CDC25B and CDC25C are believed to control mitosis entry (14). Taken together, all CDC25 phosphatases are involved in cell-cycle checkpoint regulation with redundant and non-redundant functions (9). Recently, frequent mutation of CDC25C has been reported in patients with familial platelet disorder (FPD). CDC25C defines a preleukemic clone, which eventually acquires additional mutations during disease progression. Of note, the observed CDC25C mutations are exclusively found in FPD patients rather than in de novo AML or myelodysplastic syndromes (MDSs) (15). Here, we provide first evidence that FLT3-ITD induces aberrant phosphorylation of CDC25C that functionally mimics features observed in the mutant CDC25C isoforms of FPD patients. 6249Τhis article is freely accessible online. ANTICANCER RESEARCH 36: 6249-6258 (2016) Mat...

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“…17,23 At diagnosis there was minimal discordance between standard karyotyping and FISH (4%). But surprisingly, at 18 months post-diagnosis, 84 of 267 patients (31%) showed del(5q) by karyotyping, but not by FISH.…”

Section: Importance Of the Methods Of Genetic Monitoringmentioning

confidence: 99%

Clonal evolution in myelodysplastic syndromes with isolated del(5q): the importance of genetic monitoring

Jädersten¹,

Karsan²

2011

Haematologica

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Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

Cited by 17 publications

References 20 publications

Monitoring of the Clonal Fraction by Fluorescence In Situ Hybridization in Myelodysplastic Syndrome: Comparison With International Working Group Treatment Response Criteria

Monitoring of the Clonal Fraction by Fluorescence In Situ Hybridization in Myelodysplastic Syndrome: Comparison With International Working Group Treatment Response Criteria

Kinomics Screening Identifies Aberrant Phosphorylation of CDC25C in FLT3-ITD-positive AML

Clonal evolution in myelodysplastic syndromes with isolated del(5q): the importance of genetic monitoring

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