Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells.
Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells.
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在小鼠慢性淋巴细胞性白血病中，染色体区域的丧失与人类13q14的同步13q14发生，该白血病源自早期生成的B-1 B细胞。
DOI：
10.1038/leu.2016.61
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发表时间：
2016-07
期刊：
影响因子：
11.4
通讯作者：
Hardy RR
中科院分区：
文献类型：
--
作者：
Hayakawa K;Formica AM;Colombo MJ;Shinton SA;Brill-Dashoff J;Morse Iii HC;Li YS;Hardy RR
B 细胞慢性淋巴细胞白血病 (CLL) 的一个共同特征是 13q14 染色体缺失，该染色体含有控制 B 细胞增殖的 miR15a/16-1 位点。然而，CLL 病因仍不清楚。 CLL 是一种成人白血病，其发病率随着年龄的增长而增加。 CLL 的一个独特特征是 B 细胞抗原受体 (BCR) 的使用偏向、自身反应性与多反应性以及 CD5 表达，所有这些都表明 BCR 在驱动 CLL 发病机制中发挥着作用。在人类 CLL 中，与非肌肉肌球蛋白 IIA (AMyIIA) 发生自身反应的 BCR 是复发性的。在这里，我们在小鼠中鉴定出未突变的 AMyIIA BCR，其独特的 CDR3 片段能够促进白血病发生。具有该 AMyIIA BCR 的 B 细胞是在 B-1 胎儿/新生儿发育过程中通过 CD5 诱导通过 BCR 依赖性信号传导产生的，但在成人中则不然。这些早期生成的 AMyIIA B1 B 细胞会自我更新，在衰老过程中增加，并可发展为单克隆 B 细胞淋巴细胞增多症，随后在老年小鼠中出现侵袭性 CLL，通常会丢失包含不同长度 miR15a/16-1 基因座的染色体区域，如人类 CLL。因此，B1 B 细胞产生这种确定的自身反应性 BCR 的能力是小鼠的关键诱发步骤，可促进慢性白血病的进展。
A common feature of B cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B cell antigen receptor (BCR) usage, autoreactivity with polyreactivity, and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults. These early-generated AMyIIA B1 B cells self-renew, increase during aging, and can progress to become monoclonal B cell lymphocytosis, followed by aggressive CLL in aged mice, often with loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL. Thus, the ability to generate this defined autoreactive BCR by B1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia.
影响因子：
15.3
作者：
Mageed, R A;MacKenzie, L E;Stevenson, F K;Yuksel, B;Shokri, F;Maziak, B R;Jefferis, R;Lydyard, P M
通讯作者：
Lydyard, P M