Li Wei-Yang, Sun Ai-Ning, Wu De-Pei
First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
Zhonghua Xue Ye Xue Za Zhi. 2008 Dec;29(12):797-801.
To evaluate the prevalence of c-kit and JAK2 gene mutations in protein tyrosine kinase (PTK) family in adult t(8;21) acute myeloid leukemia (AML) and their implications.
Genomic DNAs from 78 t(8;21) AML patients were screened for mutated c-kit (mutKIT) in exon 8 and 17 by PCR and sequencing. JAK2 V617F mutation screening was processed by allele-specific PCR.
(1) Among 78 t(8;21) AML patients, 27 (34.6%) had muc-kit/JAK2 and 6 (7.7%) had JAK2 V617F, and none had both. (2) Peripheral WBC count was higher in mutKIT/JAK2 V617F patients than in wide-type c-kit/JAK2 (wtKIT/JAK2) patients [(36.2 +/- 37.7) x 10(9)/L vs (21.7 +/- 21.1) x 10(9)/L] (P < 0.05). There was no significant difference in hemoglobin level, platelet counts, percentage of blast cell in bone marrow, CD117 expression level, the age of onset and gender between the two groups. Peripheral WBC count was higher in mutKIT patients [(38.8 +/- 40.7) x 10(9)/L] than in wtKIT patients [(22.0 +/- 20.4) x 10(9)/L] (P < 0.05). (3) Complete remission (CR) rates between patients with mutkit/JAK2 V617F and with wtKIT/JAK2 were similar (69.6% vs 80.0%, P > 0.05), but the 2 year continuous CR (CCR) rate was lower in patients with mutKIT/JAK2 V617F (26.7% vs 56.1%, P < 0.05). However, there was no significant difference in OS between mutKIT/JAK2 V617F and wtKIT/JAK2 patients (34.8% vs 58.6%, P > 0.05).
Occurrence of c-kit and JAK2 gene mutations especially c-kit mutation is common in t(8;21) AML patients, and is associated with higher WBC. These mutations confer higher relapse risk and predict poor prognosis.
评估成人t(8;21)急性髓系白血病（AML）中蛋白酪氨酸激酶（PTK）家族c-kit和JAK2基因突变的发生率及其意义。
采用聚合酶链反应（PCR）和测序技术，对78例t(8;21) AML患者的基因组DNA进行第8和17外显子c-kit突变（mutKIT）筛查。采用等位基因特异性PCR进行JAK2 V617F突变筛查。
（1）78例t(8;21) AML患者中，27例（34.6%）有muc-kit/JAK2突变，6例（7.7%）有JAK2 V617F突变，无患者同时存在两种突变。（2）mutKIT/JAK2 V617F患者的外周血白细胞计数高于野生型c-kit/JAK2（wtKIT/JAK2）患者[（36.2±37.7）×10⁹/L对（21.7±21.1）×10⁹/L]（P<0.05）。两组患者的血红蛋白水平、血小板计数、骨髓原始细胞百分比、CD117表达水平、发病年龄及性别差异均无统计学意义。mutKIT患者的外周血白细胞计数[（38.8±40.7）×10⁹/L]高于wtKIT患者[（22.0±20.4）×10⁹/L]（P<0.05）。（3）mutkit/JAK2 V617F患者与wtKIT/JAK2患者的完全缓解（CR）率相似（69.6%对80.0%，P>0.05），但mutKIT/JAK2 V617F患者的2年持续完全缓解（CCR）率较低（26.7%对56.1%，P<0.05）。然而，mutKIT/JAK2 V617F患者与wtKIT/JAK2患者的总生存期（OS）差异无统计学意义（34.8%对58.6%，P>0.05）。
c-kit和JAK2基因突变尤其是c-kit突变在t(8;21) AML患者中常见，且与白细胞计数升高有关。这些突变会导致更高的复发风险并提示预后不良。
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