Association of unbalanced translocation der(1;7) with germline GATA2 mutations

Kozyra, Emilia J; Göhring, Gudrun; Hickstein, Dennis D.; Calvo, Katherine R.; DiNardo, Courtney D.; Dworzak, Michael; Haas, Valérie de; Starý, Jan; Hasle, Henrik; Shimamura, Akiko; Fleming, Mark D.; Inaba, Hiroto; Lewis, Sara; Hsu, Amy P.; Holland, Steven M.; Arnold, Danielle E.; Mecucci, Cristina; Keel, Siobán; Bertuch, Alison A.; Tawana, Kiran; Barzilai‐Birenboim, Shlomit; Hirabayashi, Shinsuke; Onozawa, Masahiro; Lei, Shaohua; Alaiz, Helena; Andrikovics, Hajnalka; Betts, David R.; Beverloo, H. Berna; Buechner, Jochen; Čermák, Martin; Cervera, José; Haus, Olga; Jahnukainen, Kirsi; Manola, Kalliopi N.; Nebral, Karin; Pasquali, Francesco; Tchinda, Joëlle; Turkiewicz, Dominik; Roy, Nadine Van; Zemanová, Zuzana; Pastor, Víctor; Strahm, Brigitte; Nöllke, Peter; Niemeyer, Charlotte M.; Schlegelberger, Brigitte; Yoshimi, Ayami; Wlodarski, Marcin W.

doi:10.1182/blood.2021012781

Cited by 14 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, the association between der(1;7) and GATA2 deficiency was reiterated in a recent study by Kozyra and colleagues, demonstrating the majority (73%) of primary MDS with der(1;7) have an underlying GATA2 deficiency 120 . Isolated trisomy 8 is the second most common aneuploidy in GATA2 mutation carriers, occurring in approximately 20% of the cases 1,3–6,17,20,98 .…”

Section: Somatic Aberrations In Myeloid Malignancies With Gata2 Predi...mentioning

confidence: 76%

“…4,118,119 Similarly, the association between der(1;7) and GATA2 deficiency was reiterated in a recent study by Kozyra and colleagues, demonstrating the majority (73%) of primary MDS with der(1;7) have an underlying GATA2 deficiency. 120 Isolated trisomy 8 is the second most common aneuploidy in GATA2 mutation carriers, occurring in approximately 20% of the cases. 1,[3][4][5][6]17,20,98 Other cytogenetic events, such as trisomy 21, 1,97,121 have also been encountered alone (isolated) or in combination with other aberrations; however, due to the lack of routine screening their prevalence is largely unknown to date.…”

Section: Som At Ic a Be R R At Ions I N M Y E Loid M A Ligna Ncie S W...mentioning

confidence: 99%

See 1 more Smart Citation

GATA2 deficiency and MDS/AML: Experimental strategies for disease modelling and future therapeutic prospects

et al. 2022

Self Cite

View full text Add to dashboard Cite

The importance of predisposition to leukaemia in clinical practice is being increasingly recognized. This is emphasized by the establishment of a novel WHO disease category in 2016 called "myeloid neoplasms with germline predisposition". A major syndrome within this group is GATA2 deficiency, a heterogeneous immunodeficiency syndrome with a very high lifetime risk to develop myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). GATA2 deficiency has been identified as the most common hereditary cause of MDS in adolescents with monosomy 7. Allogenic haematopoietic stem cell transplantation is the only curative option; however, chances of survival decrease with progression of immunodeficiency and MDS evolution. Penetrance and expressivity within families carrying GATA2 mutations is often variable, suggesting that co-operating extrinsic events are required to trigger the disease. Predictive tools are lacking, and intrafamilial heterogeneity is poorly understood; hence there is a clear unmet medical need. On behalf of the ERAPerMed GATA2 HuMo consortium, in this review we describe the genetic, clinical, and biological aspects of familial GATA2-related MDS, highlighting the importance of developing robust disease preclinical models to improve early detection and clinical decision-making of GATA2 carriers.

show abstract

Section: Somatic Aberrations In Myeloid Malignancies With Gata2 Predi...mentioning

confidence: 76%

Section: Som At Ic a Be R R At Ions I N M Y E Loid M A Ligna Ncie S W...mentioning

confidence: 99%

GATA2 deficiency and MDS/AML: Experimental strategies for disease modelling and future therapeutic prospects

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…All were retrospective cohorts: 9 reported in articles, 2 in letters, 7,9 1 in abstract 13 . Five cohorts were from multiple centers 6,9,10,13,20 . Of the 9 studies reported in articles, 3 had low and 6 intermediate risk of bias according to NOS (Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…[3][4][5] The recently identified unbalanced translocation der(1;7) (q10;p10)[der(1;7)], a rare chromosomal abnormality seen in myeloid neoplasms, 6,7 involves fusion of the entire 1q arm to the 7p arm at the centromeric regions, resulting in monosomy 7q and 1q gain. 8 Studies find der(1;7) in 0.58%-2.59% of myelodysplastic syndrome (MDS) cases, 7,9,10 0.2%-2% of acute myeloid leukemia (AML) cases, and about 1% of myeloproliferative neoplasms (MPN). 11 Most der(1;7) cases are MDS (58%), followed by AML (26%) and MPN (9%).…”

Section: Introductionmentioning

confidence: 99%

The der(1;7)(q10;p10) defining a distinct profile from −7/del(7q) in myelodysplastic syndromes: A systematic review and meta‐analysis

Lang,

Luo,

Wang

et al. 2024

Cancer Medicine

View full text Add to dashboard Cite

Background and ObjectiveMyelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like −7/del(7q). However, knowledge of der(1;7)'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of −7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta‐analyses comparing der(1;7) to −7/del(7q).MethodsPublications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random‐effects models. Publication bias was evaluated and sensitivity analyses were performed.ResultsThe comparative meta‐analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than −7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than −7, lower absolute neutrophil counts, and higher percentage of patients with non‐excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with −7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co‐occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less −5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than −7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37).ConclusionThe findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from −7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.

show abstract

“…The primary endpoint was the overall survival (OS), and the secondary endpoints were the leukemia‐free survival (LFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM). The following karyotypic descriptions were considered as der(1;7)(q10;p10): +1, der(1;7)(q10;p10); der(1;7)(q10;p10); +1, der(1;7); der(7)t(1;7)(q11;p11), as previously reported [ 12 ]. Cases with chromosomal changes in addition to der(1;7) or ‐7/del(7q) were defined as having additional chromosomal abnormalities (ACAs).…”

Section: Introductionmentioning

confidence: 99%

Outcomes after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with der(1;7)(q10;p10)

Mizumaki

Ishiyama

Aoki³

et al. 2022

eJHaem

View full text Add to dashboard Cite

The prognosis of acute myeloid leukemia (AML) patients with der(1;7)(q10;p10) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) is unclear due to its rarity. We retrospectively analyzed 151 AML patients with der(1;7)(q10;p10) and compared the findings with those of 853 AML patients with monosomy 7 or chromosome 7q deletion (-7/del(7q)) using Japanese nationwide registry data.The der(1;7)(q10;p10) group showed significantly better transplant outcomes thanThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Association of unbalanced translocation der(1;7) with germline GATA2 mutations

Abstract: Schmugge (Switzerland) -provided clinical and cytogenetic information about patients as well as primary material. Coordinating

Cited by 14 publications

References 28 publications

GATA2 deficiency and MDS/AML: Experimental strategies for disease modelling and future therapeutic prospects

GATA2 deficiency and MDS/AML: Experimental strategies for disease modelling and future therapeutic prospects

The der(1;7)(q10;p10) defining a distinct profile from −7/del(7q) in myelodysplastic syndromes: A systematic review and meta‐analysis

Outcomes after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with der(1;7)(q10;p10)

Contact Info

Product

Resources

About