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Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.
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三氧化二砷治疗急性早幼粒细胞性白血病研究进展
砷是一种广泛分布于自然界的非金属元素,在地表元素构成中居第20位.自然界存在的砷通常以化合物的形式存在.常见的砷化合物有三氧化二砷(As2O3,俗称砒霜),雄黄(As2S2)和雌黄(As2S3)等.元素砷几乎无毒.将元素状态的砷作为一种强壮剂,服用可以强身壮体御寒.微量的砷化合物对人体也是无害的.自古以来,一些药物和美容化妆品中都含有适量的砷.但是,一旦人体摄入过量砷化合物,尤其是三价砷化合物,便会导致砷中毒.急性砷中毒会严重损害胃肠道、呼吸、神经系统等,严重者可出现昏迷、呼吸困难、心力衰竭甚至死亡.慢性砷中毒主要表现为皮肤改变和某些周围神经系统症状.极少数长期慢性砷中毒病人可能进一步发生癌症.这些砷毒性主要是由于它与巯基的强亲和力.它与含巯基的酶结合后,抑制酶活性进而扰乱正常生理功能,因为这些酶常常涉及三羧酸循环、ATP的产生及氧化磷酸化过程.砷还可通过抑制谷胱甘肽(GSH)等抗氧化酶的活性而产生氧化损伤.此外,砷也可能干扰DNA聚合酶,影响细胞DNA合成和修复.
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全反式维A酸诱导分化治疗急性早幼粒细胞白血病的机制研究
1985年,我所于体外研究证明,全反式维A酸(ATRA)可以诱导HL-60及新鲜APL细胞向终末成熟细胞分化.1986年我所在国际上首先应用ATRA治疗APL 24例,23例取得完全缓解(CR).该结果发表在Blood(1988,72:567),并在以后的年代里,得到国内外广泛的证实.进一步的临床研究结果指出,APL用ATRA与化疗合理组合治疗,CR率可提高到90%~95%[1].我所已在1999年总结了临床应用的十年经验[2].
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单管多重检测急性早幼粒细胞白血病 PML-RARa 融合基因3种剪切体 RT-qPCR 方法的建立及临床应用
本刊主编,武汉大学人民医院李艳教授(通讯作者)指导博士研究生陈占国(第一作者)等在《PLOS ONE》(2015,10(3) e0122530,IF:3.534)发表了题为“Development and validation of a 3-plex RT-qPCR assay for the simultaneous detection and quantitation of the three PML-RARa fusion transcripts in acute promyelocytic leukemia”的研究论文,主要内容如下。