Il-1r1 drives leukemogenesis induced by Tet2 loss.
Il-1r1 drives leukemogenesis induced by Tet2 loss.
复制标题
DOI：
10.1038/s41375-022-01665-3
复制
发表时间：
2022-10
期刊：
影响因子：
11.4
通讯作者：
Kapur R
中科院分区：
文献类型：
--
作者：
Burns SS;Kumar R;Pasupuleti SK;So K;Zhang C;Kapur R
（Tet 2）基因，通常在血液恶性肿瘤中发生突变，使炎症通路（包括白细胞介素-1（IL-1）通路）失调[1-3]。已经报道了IL-1信号传导在终末分化的造血细胞和非细胞自主环境中的作用[3，4]。然而，我们的研究小组证明，抑制炎症通路可以抑制克隆造血（CH），表明造血干细胞和祖细胞（HSPC）在炎症中的潜在直接作用[5]。由于TET 2突变通常存在于HSPC中并为这些细胞提供竞争优势，HSPC中IL-1通路的失调可能有助于白血病发生并可能催化白血病前期状态进展为恶性肿瘤[6] AET 2基因突变在多种骨髓恶性肿瘤中检测到，包括急性髓性白血病（AML）[6]。同样，Tet 2 −/−转基因小鼠和Tet 2 −/−骨髓（BM）移植受体小鼠表现出脾肿大、单核细胞增多、髓外造血和Lin-; Sca 1 +; c-Kit+（LSK）群体扩增[7]。急性和慢性IL-1暴露以淋巴样细胞为代价扩增骨髓细胞;然而，慢性暴露最终耗尽造血干细胞（HSC）自我更新的能力[8]。虽然先前的研究已经研究了IL-1α和IL-1β对造血和成熟造血细胞的外源性作用，但IL-1 R1（10种IL-1受体中的主要受体）结合多种蛋白质，包括IL-1α、IL-1β、IL-1受体拮抗剂、IL-38及其共受体IL-1受体辅助蛋白，强调HSPC中IL-1 R1依赖性信号传导的全部结果尚不清楚[9]。
(Tet2) gene, which is commonly mutated in hematological malignancies, dysregulates inflammatory pathways, including the interleukin-1 (IL-1) pathway [1-3]. Roles for IL-1 signaling have been reported in terminally differentiated hematopoietic cells and in non-cell autonomous contexts [3, 4]. However, our group demonstrated that inhibition of inflammatory pathways can suppress clonal hematopoiesis (CH), indicating potential direct roles for hematopoietic stem and progenitor cells (HSPCs) in inflammation [5]. As TET2 mutations are often present in HSPCs and provide these cells with a competitive advantage, dysregulation of the IL-1 pathway in HSPCs may contribute to leukemogenesis and may catalyze the progression of preleukemic states to malignancy [6].Mutations in the TET2 gene are detected in a variety of myeloid malignancies, including acute myeloid leukemia (AML)[6]. Similarly, Tet2−/− transgenic mice and recipient mice transplanted with Tet2−/− bone marrow (BM) exhibit splenomegaly, monocytosis, extramedullary hematopoiesis, and expansion of the Lin-; Sca1+; c-Kit+(LSK) population [7]. Acute and chronic IL-1 exposure expands myeloid cells at the expense of lymphoid cells; however, chronic exposure ultimately depletes the ability of hematopoietic stem cells (HSCs) to self-renew [8]. While previous studies have investigated the exogenous effects of IL-1α and IL-1β on hematopoiesis and on mature hematopoietic cells, IL-1R1, the primary of ten IL-1 receptors, binds to multiple proteins, including IL-1α, IL-1β, IL-1 receptor antagonist, IL-38, and its co-receptor IL-1 receptor accessory protein, underscoring that the full spectrum of the consequences of IL-1R1-dependent signaling in HSPCs is not yet known [9].
登录
查看更多内容
影响因子：
7.5
作者：
Vucinic V;Ruhnke L;Sockel K;Röhnert MA;Backhaus D;Brauer D;Franke GN;Niederwieser D;Bornhäuser M;Röllig C;Platzbecker U;Schwind S;Jentzsch M
通讯作者：
Jentzsch M
DOI：
10.4049/jimmunol.181.11.7507
发表时间：
2008-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kumar R;Fossati V;Israel M;Snoeck HW
通讯作者：
Snoeck HW
影响因子：
8.8
作者：
Carey A;Edwards DK 5th;Eide CA;Newell L;Traer E;Medeiros BC;Pollyea DA;Deininger MW;Collins RH;Tyner JW;Druker BJ;Bagby GC;McWeeney SK;Agarwal A
通讯作者：
Agarwal A
影响因子：
2.6
作者：
Cull, Alyssa H.;Snetsinger, Brooke;Rauh, Michael J.
通讯作者：
Rauh, Michael J.
影响因子：
5.4
作者：
Kaner, Justin;Desai, Pinkal;Hassane, Duane C.
通讯作者：
Hassane, Duane C.