Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression

Hahm, Chorong; Huh, Hee Jin; Mun, Yeung Chul; Seong, Chu-Myong; Chung, Wha Soon; Huh, Jungwon

doi:10.1111/ijlh.12257

Cited by 11 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we had a low detection rate of CNVs (37.5%) compared to other studies (44-69%) [Tefferi et al, 2008;Rumi et al, 2011;Brecqueville et al, 2014;Hahm et al, 2015]. We could not identify any clinical bias between our study and those described in the literature that could reasonably explain this discrepancy.…”

Section: Discussioncontrasting

confidence: 80%

“…JAK2 plays an important role in cell signaling and proliferation [Campbell et al, 2006;Tefferi et al, 2009;Vainchenker et al, 2017]. Mutations in this gene confer constitutive activation of the JAK-STAT and related pathways, promoting differentiation and proliferation of different cell lineages [Hahm et al, 2015]. It is still not understood whether the JAK2 mutation is the first event in myeloproliferative neoplasms or secondary to other genetic and epigenetic events [Campbell et al, 2006;Tefferi et al, 2008Tefferi et al, , 2009.…”

Section: Discussionmentioning

confidence: 99%

“…The GATA family is essential to the development of many cell lineages, including hematopoietic, cardiac, and endodermal. GATA1 , GATA2 , and GATA3 are needed for normal hematopoiesis, and their mutations are implicated on a variety of blood disorders, including MF [Dos Santos et al, 2011;Hahm et al, 2015;Mehrotra et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

“…These defects are attributed to mitotic recombination in somatic cells and have been recognized in a variety of neoplasms [O'Keefe et al, 2010;Visani et al, 2011;Hahm et al, 2015].…”

mentioning

confidence: 99%

“…Implementation of chromosomal microarrays in MF have been reported in few studies with a detection rate of imbalances of 44% [Tefferi et al, 2008], 69% [Rumi et al, 2011], 54% [Brecqueville et al, 2014], and 56% [Hahm et al, 2015]. However, most of the abovementioned used array-CGH platforms without SNPs and therefore were unable to detect CN-LOHs.…”

mentioning

confidence: 99%

See 4 more Smart Citations

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

Paula

Nonino²,

Nascimento³

et al. 2018

Cytogenet Genome Res

View full text Add to dashboard Cite

Myelofibrosis is the rarest and most severe type of Philadelphia-negative classical myeloproliferative neoplasms. Although mutually exclusive driver mutations in JAK2, MPL, or CALR that activate JAK-STAT pathway have been related to the pathogenesis of the disease, chromosome abnormalities have also been associated with the phenotype and prognosis of the disease. Here, we report the use of a chromosomal microarray platform consisting of both oligo and SNP probes to improve the detection of chromosome abnormalities in patients with myelofibrosis. Sixteen patients with myelofibrosis were tested, and the results were compared to karyotype analysis. Driver mutations in JAK2, MPL, or CALR were investigated by PCR and MLPA. Conventional cytogenetics revealed chromosome abnormalities in 3 out of 16 cases (18.7%), while chromosomal microarray analysis detected copy-number variations (CNV) or copy-neutral loss of heterozygosity (CN-LOH) alterations in 11 out of 16 (68.7%) patients. These included 43 CN-LOH, 14 deletions, 1 trisomy, and 1 duplication. Ten patients showed multiple chromosomal abnormalities, varying from 2 to 13 CNVs or CN-LOHs. Mutational status for JAK2, CALR, and MPL by MLPA revealed a total of 3/16 (18.7%) patients positive for the JAK2 V617F mutation, 9 with CALR deletion or insertion and 1 positive for MPL mutation. Considering that most of the CNVs identified were smaller than the karyotype resolution and the high frequency of CN-LOHs in our study, we propose that chromosomal microarray platforms that combine oligos and SNP should be used as a first-tier genetic test in patients with myelofibrosis.

show abstract

Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…These defects are attributed to mitotic recombination in somatic cells and have been recognized in a variety of neoplasms [O'Keefe et al, 2010;Visani et al, 2011;Hahm et al, 2015].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

Paula

Nonino²,

Nascimento³

et al. 2018

Cytogenet Genome Res

View full text Add to dashboard Cite

show abstract

Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia

Hyrenius-Wittsten

Sturesson

Bidgoli

et al. 2016

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN‐U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39‐year‐old woman at MDS/MPN‐U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non‐silent somatic mutations, including DNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN‐U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, for example, the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs. © 2016 Wiley Periodicals, Inc.

show abstract

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

2016

Diagnostic Pathology: Molecular Oncology

View full text Add to dashboard Cite

Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression

Abstract: This study suggests sequential genomic changes identified by SNP-A may be associated with disease progression.

Cited by 11 publications

References 23 publications

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Contact Info

Product

Resources

About