Department of Hematology and Transplantology, Medical University of Gdansk, Poland.
Eur J Haematol. 2011 Jun;86(6):531-5. doi: 10.1111/j.1600-0609.2011.01598.x. Epub 2011 Apr 7.
Mastocytosis is a myeloproliferative neoplasm characterized by the excessive proliferation of mast cells. Mast cell leukaemia (MCL), the aggressive form of this disease, requires cytoreductive therapy, such as cladribine, interferon-alpha-2b and, most recently, tyrosine kinase inhibitors - dasatinib or imatinib.
We present a case of a 56-yr-old female patient with aleukaemic MCL in whom the typical KIT-D816V mutation was not detected. Sequencing of the entire coding sequence of KIT gene revealed a somatic mutation in exon 9 (p.A502_Y503dup). This mutation was previously reported in patients with gastrointestinal stromal tumours (GIST). Considering the good response to imatinib in such patients, therapy with imatinib was attempted in our patient. The treatment tolerance and outcomes were very good, with reduced mast cell infiltration of the bone marrow, normalization of the serum tryptase concentration and resolution of the clinical signs and symptoms.
In the absence of the KIT-D816V in systemic forms of mast cell proliferation, a search for other mutations is indicated, preferably by sequencing the entire KIT gene, as this can influence the choice of treatment. The finding of the p.A502_Y503dup in exon 9, a mutation which has been observed in GIST but not previously reported in any form of aggressive mastocytosis, can be associated with a good response to imatinib in both diseases.
肥大细胞增多症是一种骨髓增生性肿瘤，其特征是肥大细胞过度增殖。肥大细胞白血病（MCL）是这种疾病的侵袭性形式，需要细胞减少治疗，如克拉屈滨、干扰素-α-2b 和最近的酪氨酸激酶抑制剂 - 达沙替尼或伊马替尼。
我们报告了一例 56 岁女性患者，患有非白血病性 MCL，未检测到典型的 KIT-D816V 突变。对 KIT 基因的整个编码序列进行测序显示外显子 9 中的体细胞突变（p.A502_Y503dup）。这种突变以前在胃肠道间质瘤（GIST）患者中报道过。考虑到此类患者对伊马替尼的良好反应，尝试对我们的患者进行伊马替尼治疗。治疗耐受性和结果非常好，骨髓中肥大细胞浸润减少，血清胰蛋白酶浓度正常化，临床症状和体征得到缓解。
在系统性肥大细胞增殖缺乏 KIT-D816V 的情况下，应进行其他突变的检测，最好通过对整个 KIT 基因进行测序，因为这可能会影响治疗选择。在外显子 9 中发现 p.A502_Y503dup 突变，这种突变在 GIST 中观察到，但以前在任何侵袭性肥大细胞增多症形式中均未报道过，与两种疾病中对伊马替尼的良好反应相关。
