Ozer Ozden, Zhao Yi D, Ostler Kelly R, Akin Cem, Anastasi John, Vardiman James W, Godley Lucy A
Section of Hematopathology, Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Leuk Lymphoma. 2008 Aug;49(8):1567-77. doi: 10.1080/10428190802140865.
KIT mutations have been identified in several malignancies, including acute myeloid leukemia (AML) and systemic mastocytosis (SM). Mast cell leukemia (MCL) is the most aggressive mast cell neoplasm, but has not been well studied due to its rarity. We identified novel KIT transcripts in two patients with MCL and two patients with SM with an associated hematological disorder, but not from two patients with SM. Similar novel KIT transcripts were also observed in normal CD34+ cells from bone marrow and umbilical cord blood, suggesting that altered KIT isoforms may be specific to the blast stage of hematopoietic precursors. The novel KIT proteins lack several domains including the ATP binding site, and one was inactive in a functional test for autophosphorylation. Our discovery of novel KIT transcripts underscores the importance of analysing entire protein encoding regions when studying genes of interest.
KIT突变已在多种恶性肿瘤中被鉴定出来，包括急性髓系白血病（AML）和系统性肥大细胞增多症（SM）。肥大细胞白血病（MCL）是最具侵袭性的肥大细胞肿瘤，但由于其罕见性尚未得到充分研究。我们在两名MCL患者和两名伴有血液系统疾病的SM患者中鉴定出了新的KIT转录本，但在两名SM患者中未发现。在来自骨髓和脐带血的正常CD34+细胞中也观察到了类似的新KIT转录本，这表明改变的KIT异构体可能特定于造血前体细胞的原始阶段。新的KIT蛋白缺乏包括ATP结合位点在内的几个结构域，并且其中一个在自磷酸化功能测试中无活性。我们对新KIT转录本的发现强调了在研究感兴趣的基因时分析整个蛋白质编码区域的重要性。
