波兰慢性髓性白血病患者接受伊马替尼治疗时BCR-ABL基因突变的频率：MAPTEST研究的最终报告

Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

作者信息

Lewandowski Krzysztof, Warzocha Krzysztof, Hellmann Andrzej, Skotnicki Aleksander, Prejzner Witold, Foryciarz Kajetana, Sacha Tomasz, Gniot Michał, Majewski Mirosław, Solarska Iwona, Nowak Grazyna, Wasag Bartosz, Kobelski Mikołaj, Scibiorski Cezary, Siemiatkowski Marek, Lewandowska Maria, Komarnicki Mieczysław

机构信息

Department of Hematology, Poznan University of Medical Sciences, Poznań, Poland.

出版信息

Pol Arch Med Wewn. 2009 Dec;119(12):789-94.

PMID:20010464

Abstract

INTRODUCTION

The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment.

OBJECTIVES

The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM).

PATIENTS AND METHODS

Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM.

RESULTS

Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM.

CONCLUSIONS

The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.

摘要

引言

慢性髓性白血病（CML）患者中BCR-ABL癌基因突变的存在可能是酪氨酸激酶抑制剂治疗失败的原因。

目的

本研究的目的是评估接受伊马替尼（IM）治疗的CML患者（MAPTEST研究）中BCR-ABL基因突变的频率。

患者与方法

对92例接受IM治疗超过3个月的患者进行BCR-ABL基因的直接测序分析。IM治疗的平均时间为18个月。分析时，75例患者处于慢性期（CP），4例处于第二期CP，5例处于加速期，8例处于急变期。57例患者（62%）接受每日400mg剂量的IM治疗，35例患者接受更高剂量（每日600或800mg）治疗。纳入标准基于欧洲白血病网关于IM治疗失败和疗效欠佳的定义。

结果

92例患者中的11例检测到12种突变，包括慢性期诊断出4种突变（36.7%），加速期3种（27.3%），急变期4种（36.7%）。1例CML淋巴系急变期患者检测到F359V和Y253F共突变。在整个研究组中，5例原发性耐药患者中有2例（40%）检测到突变（M351T、F359V + Y253F），87例对IM获得性耐药的患者中有9例（10.3%）检测到突变（E255K、T315I - 3次、M351T、E355G、F359V - 2次）。