EVI1 is critical for the pathogenesis of a subset of MLL-AF9–rearranged AMLs

Bindels, Eric; Havermans, Marije; Lugthart, Sanne; Erpelinck, Claudia; Wocjtowicz, Elizabeth; Krivtsov, Andrei V.; Rombouts, Elwin; Armstrong, Scott A.; Taskesen, Erdogan; Haanstra, Jurgen R.; Beverloo, H. Berna; Döhner, Hartmut; Hudson, Wendy A.; Kersey, John H.; Delwel, Ruud; Kumar, Ashish

doi:10.1182/blood-2011-11-393827

Cited by 71 publications

(82 citation statements)

References 48 publications

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“…36 In a following study, Bindels et al showed that approximately 43% of all cases with MLL/KMT2A rearrangement are positive for EVI1 by real-time reverse transcription polymerase chain reaction, and EVI1 expression plays a critical role for the pathogenesis of a subset of AMLs with MLL-AF9 rearrangement. 37 Similar to patients with EVI1 gene rearrangements, EVI1 overexpression without 3q26.2/EVI1 translocation is also associated with poor prognosis in patients with AML. 38 In CML, Daghistani et al have shown that EVI1 overexpression is associated with imatinib resistance.…”

Section: Discussionmentioning

confidence: 97%

Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Wang¹,

Cortes

Lin³

et al. 2015

Blood

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• The emergence of 3q26.2 rearrangements in CML is associated with resistance to TKI treatment and poor prognosis.• 3q26.2 rearrangements play a predominant role in determining prognosis, irrelevant to the presence or absence of other additional chromosomal abnormalities in CML.Chromosome 3q26.2 abnormalities in acute myeloid leukemia, including inv(3)/t(3;3) and t(3;21), have been studied and are associated with a poor prognosis. Their prevalence, response to tyrosine kinase inhibitor (TKI) treatment, and prognostic significance in chronic myelogenous leukemia (CML) are largely unknown. In this study, we explored these aspects using a cohort of 2013 patients with CML diagnosed in the era of TKI therapy. Chromosome 3 abnormalities were observed in 116 (5.8%) of 2013 cases. These cases were divided into 5 distinct groups: A, inv(3)(q21q26.2)/t(3;3)(q21;q26.2), 26%; B, t(3;21)(q26.2;q22), 17%; C, other 3q26.2 rearrangements, 7%; D, rearrangements involving chromosome 3 other than 3q26.2 locus, 32%; and E, gain or loss of partial or whole chromosome 3, 18%. In all, 3q26.2 rearrangements were the most common chromosome 3 abnormalities (50%, groups A-C). 3q26.2 rearrangements emerged at different leukemic phases. For cases with 3q26.2 rearrangements that initially emerged in chronic or accelerated phase, they had a high rate of transformation to blast phase. Patients with 3q26.2 abnormalities showed a marginal response to TKI treatment, and no patients achieved a long-term sustainable response at a cytogenetic or molecular level. Compared with other chromosomal abnormalities in CML, patients with 3q26.2 rearrangements had poorer overall survival. The presence or absence of other concurrent chromosomal abnormalities did not affect survival in these patients, reflecting the predominant role of 3q26.2 rearrangements in determining prognosis. Interestingly, although heterogeneous, chromosome 3 abnormalities involving non-3q26.2 loci (groups D, E) also conferred a worse prognosis compared with changes involving other chromosomes in this cohort.

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Section: Discussionmentioning

confidence: 97%

Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Wang¹,

Cortes

Lin³

et al. 2015

Blood

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“…2,6,14,15,[28][29][30] Animal models demonstrate that forced overexpression of EVI1 results in myeloid hyperproliferation, downregulation of genes related to myeloid differentiation, and cause a fatal disorder resembling human MDS. 20,21,30,31 In humans, rare cases have been reported of myelodysplasia with monosomy 7 related to overexpression of EVI1 caused by retroviral insertional activation during gene therapy. 22 Thus, the biological importance of the inv(3)/t(3;3) in the development of myeloid malignancy is known and can be used as a unifying theme for considering AML and MDS with this abnormality as a discrete entity.…”

Section: Discussionmentioning

confidence: 99%

Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study

et al. 2014

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“…29 Cells were crosslinked at room temperature for 10 minutes with 1% formaldehyde and sonicated to shear the chromatin. Immunoprecipitation of crosslinked chromatin was performed overnight at 4°C with antibodies directed against the histone mark H3K27ac, the coactivator p300, and TFs including RUNX1, LMO2, PU.1, ERG, TAL1, and SCL, or an equal amount of isotype immunoglobulin G (IgG) as background control (http://149.171.101.136/python/ BloodChIP/search.html).…”

Section: Chip Sequencingmentioning

confidence: 99%

An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation

Avellino¹,

Havermans²,

Erpelinck³

et al. 2016

Blood

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EVI1 is critical for the pathogenesis of a subset of MLL-AF9–rearranged AMLs

Abstract: The proto-oncogene EVI1 (ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements.

Cited by 71 publications

References 48 publications

Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study

An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation

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