Lack of KIT or FMS internal tandem duplications but co-expression with ligands in AML
Lack of KIT or FMS internal tandem duplications but co-expression with ligands in AML
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DOI：
10.1016/s0145-2126(03)00184-x
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发表时间：
2004-02-01
影响因子：
2.7
通讯作者：
Small, D
中科院分区：
文献类型：
--
作者：
Zheng, R;Klang, K;Small, D
KIT和FMS是III类受体酪氨酸激酶家族的成员，在正常造血细胞上表达，并且在正常造血中具有重要作用。FLT 3也是III类受体酪氨酸激酶家族的成员，在造血干细胞/祖细胞、NK细胞和树突状细胞中发挥重要作用。近年来，在急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者表达的FLT 3受体的跨膜（JM）区域发现了内部串联重复（ITDs）突变。突变导致受体的组成性二聚化和活化，从而促进白血病转化。KIT和FMS也经常在AML中表达，并与FLT 3密切相关。因此，AML患者的KIT和/或FMS基因中也可能发生类似的ITD突变。为了探索这种可能性，通过逆转录聚合酶链反应（RT-PCR）检查了13个人白血病淋巴瘤细胞系和44个急性髓细胞白血病患者样本，以确定KIT或FMS受体JM区域是否存在ITD突变。13个人白血病-淋巴瘤细胞系或44个AML原代骨髓样本均未在涉及FLT 3突变的JM区域的KIT或FMS中表达ITD。还检查了13个细胞系和44个AML样本中KIT和/或FMS受体与其各自配体的可能共表达，正如我们在FLT 3及其配体FL中所看到的那样。这种共表达可能有助于白血病通过自分泌、旁分泌转化或内分泌激活机制。6/13的细胞系和27/44的原发性AML样品显示KIT受体和配体（SCF）的共表达，而10/13的细胞系和35/44的原发性AML样品显示FMS受体和配体（CSF-1）的共表达。因此，虽然未发现ITD突变，但KIT和/或FMS与其各自配体共表达的结果表明，这些受体可能通过自分泌、旁分泌或内分泌相互刺激促进某些AML患者的白血病发生。(C)2003爱思唯尔有限公司。保留所有权利。
KIT and FMS, members of the class III receptor tyrosine kinase family, are expressed on normal hematopoietic cells and have important roles in normal hematopoiesis. FLT3 is also a member of the class III receptor tyrosine kinase family and plays important role in hematopoietic stem/progenitor cells, NK, and dendritic cells. Recently, internal tandem duplication (ITDs) mutations have been found in the juxtamembrane (JM) region of FLT3 receptor expressed by patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The mutations result in the constitutive dimerization and activation of the receptor, contributing to leukemic transformation. KIT and FMS are also frequently expressed in AML and are closely related to FLT3. Thus, similar ITD mutations could also occur in the KIT and/or FMS gene of patients with AML. To explore this possibility, 13 human leukemia-lymphoma cell lines and 44 AML patient samples were examined by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of ITD mutations in the JM region of the KIT or FMS receptor. None of the 13 human leukemia-lymphoma cell lines or 44 AML primary bone marrow samples express ITDs in either KIT or FMS in the JM region that is involved in FLT3 mutations. The 13 cell lines and 44 AML samples were also examined for the possible co-expression of KIT and/or FMS receptors with their respective ligands, as we have seen for FLT3 and its ligand, FL. This co-expression could contribute to leukemic transformation through autocrine, paracrine, or intracrine activation mechanisms. And 6/13 cell lines and 27/44 primary AML samples exhibit co-expression of the KIT receptor and ligand (SCF) while 10/13 cell lines and 35/44 primary AML samples exhibit co-expression of the FMS receptor and ligand (CSF-1). Therefore, while ITD mutations were not found, the findings of co-expression of KIT and/or FMS with their respective ligands implies these receptors might contribute to leukemogenesis in some patients with AML through autocrine, paracrine, or intracrine interactive stimulation. (C) 2003 Elsevier Ltd. All rights reserved.