High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)

Kuipers, Jenny E; Coenen, Eva A.; Balgobind, Brian V.; Starý, Jan; Baruchel, André; Haas, Valérie de; Bont, Eveline S.J.M. de; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Cloos, Jacqueline; Oorschot, Astrid A Danen-van; Boer, Monique L. den; Marschalek, Rolf; Meyer, Claus; Pieters, Rob; Zwaan, C. Michel; Heuvel‐Eibrink, Marry M. van den

doi:10.1182/blood-2010-05-286138

Cited by 19 publications

(19 citation statements)

References 30 publications

(33 reference statements)

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“…66 In addition, overexpression of IGSF4, by epigenetic regulation, was discovered in cases with a t(9;11)(p22;q23) and FAB-M5 morphology, a subgroup with a relatively favorable outcome. 105 The exact role of these genes in the leukemogenesis of MLL-rearranged AML needs to be further elucidated. It would be of importance to identify mutations or aberrant expression of specific genes or signaling pathways that are involved in those subtypes with a poor outcome, for example, t(6;11)(q27;q23).…”

Section: Mll-rearrangementmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

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Section: Mll-rearrangementmentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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“…In addition to the patient's initial response to treatment, its prognosis is largely determined by the presence of cytogenetic abnormalities and genetic lesions. [1][2][3][4][5][6] Several recurrent cytogenetic abnormalities, such as 11q23/MLLrearrangements, predict outcome in myeloid neoplasms and acute leukemia. 7 So far, Ͼ 60 different translocation partners (TPs) have been identified, and new partners are still being reported to add to the diversity of MLL-rearranged leukemia.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study

Coenen

Raimondi

Harbott

et al. 2011

Blood

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We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLLrearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n ‫؍‬ 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P ‫؍‬ .003; Cox model for OS hazard ratio (HR) 0.54, P ‫؍‬ .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n ‫؍‬ 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P ‫؍‬ .04; OS 24% vs 50%, P < .001; HR 1.77, P ‫؍‬ .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P ‫؍‬ .01).Complex karyotype, defined as > 3 abnormalities, was present in 26% (n ‫؍‬ 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P ‫؍‬ .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied. (Blood. 2011;117(26):7102-7111)

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“…Inactivation of the TSLC1 gene, which leads to the suppression of Necl-2 expression, has been frequently described in various human cancers, including lung, cervical, and breast cancers (38). Conversely, Necl-2 was found to be expressed de novo in adult T leukemia or overexpressed in certain other tumors (39)(40)(41)(42)(43). Thus, similar to tumor-associated molecules, such as FasL or PD-L1, Necl-2 in tumor cells may represent a new tumor counterattack mechanism to evade immunosurveillance by Vg9Vd2 T cells (44).…”

Section: Discussionmentioning

confidence: 99%

CRTAM Receptor Engagement by Necl-2 on Tumor Cells Triggers Cell Death of Activated Vγ9Vδ2 T Cells

Dessarthe

Thedrez

Latouche

et al. 2013

The Journal of Immunology

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Human Vγ9Vδ2 T cells exert potent in vitro and in vivo antitumor activities, making them promising candidates for immunotherapy strategies. Recognition of tumor cells by Vγ9Vδ2 T cells requires engagement of the TCR and/or NK receptors. Recently, one of the novel NK receptors, the class I–restricted T cell–associated molecule (CRTAM), has been described to promote cytotoxic function of NK cells and to lead to IFN-γ secretion by CD8+ T cells through interaction with its ligand, Necl-2. A better understanding of the role of CRTAM in Vγ9Vδ2 T cell functions is highly relevant to optimize innate-like T cell–based cancer immunotherapy. In this article, we report that CRTAM is transiently expressed on activated Vγ9Vδ2 T lymphocytes following TCR engagement. However, CRTAM–Necl-2 interaction does not modify the cytotoxic function or IFN-γ secretion of Vγ9Vδ2 T cells. The expression of CRTAM in activated Vγ9Vδ2 T cells is quickly downregulated following interaction with Necl-2 on tumor cells. Of interest, CRTAM is concurrently acquired at the cell surface of Necl-2+ tumor cells through Vγ9Vδ2 T cell membrane capture. Finally, we highlight that coculture experiments with tumor cells expressing Necl-2 result in significant cell death of CRTAM+ Vγ9Vδ2 T cells. CRTAM-mediated cell death is dependent on an autophagic process, but not on apoptosis or necroptosis, as attested by the expression of characteristic markers and blocking experiments with specific inhibitors. On the basis of these findings, we propose that Necl-2 on tumor cells represents a new tumor counterattack mechanism and a potential target to improve efficiency of γδ T cell–based immunotherapy.

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High IGSF4 expression in pediatric M5 acute myeloid leukemia with t(9;11)(p22;q23)

Cited by 19 publications

References 30 publications

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study

CRTAM Receptor Engagement by Necl-2 on Tumor Cells Triggers Cell Death of Activated Vγ9Vδ2 T Cells

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