Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions.
Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions.
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DOI：
10.1016/j.blre.2021.100825
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发表时间：
2021-09
期刊：
影响因子：
7.4
通讯作者：
Deininger MW
中科院分区：
文献类型：
--
作者：
Osman AEG;Deininger MW
慢性髓系白血病(CML)是一种骨髓增生性肿瘤，由相互易位[t(9；22)(q34；q11.2)]引起，该易位导致bcr基因序列(22q11)下游的abl1基因序列(9q34)融合，在细胞遗传学上可见Philadelphia染色体(Ph)。由此产生的BCR/ABL1嵌合蛋白是一种具有结构性活性的酪氨酸激酶，它激活了多个信号通路，这些信号通路共同导致恶性转化。在慢性粒细胞白血病(CP-CML)的早期(慢性期)，髓系细胞室扩大，但分化保持不变。如果没有有效的治疗，慢性粒细胞白血病总是进展到急性期(BP-CML)，这是一种髓系或淋巴系表型的急性白血病。BCR-AB1酪氨酸激酶抑制剂(TKIs)的开发彻底改变了慢性粒细胞白血病的治疗方法，开启了肿瘤学的新纪元。随着三代BCR/ABL1 TKIs今天获得批准，大多数CML患者享有长期缓解和接近正常预期寿命。然而，只有少数患者在TKI停止后保持缓解，这种状态被称为治疗自由缓解(TFR)。不幸的是，5-10%的患者由于耐药而未能通过TKIs，并有发展为BP-CML的风险，这种疾病只有通过造血干细胞移植才能治愈。克服TKI耐药、改善BP-CML预后、提高TFR率是CML研究的热点。
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by a reciprocal translocation [t(9;22)(q34;q11.2)] that leads to the fusion of ABL1 gene sequences (9q34) downstream of BCR gene sequences (22q11) and is cytogenetically visible as Philadelphia chromosome (Ph). The resulting BCR/ABL1 chimeric protein is a constitutively active tyrosine kinase that activates multiple signaling pathways, which collectively lead to malignant transformation. During the early (chronic) phase of CML (CP-CML), the myeloid cell compartment is expanded, but differentiation is maintained. Without effective therapy, CP-CML invariably progresses to blast phase (BP-CML), an acute leukemia of myeloid or lymphoid phenotype. The development of BCR-AB1 tyrosine kinase inhibitors (TKIs) revolutionized the treatment of CML and ignited the start of a new era in oncology. With three generations of BCR/ABL1 TKIs approved today, the majority of CML patients enjoy long term remissions and near normal life expectancy. However, only a minority of patients maintain remission after TKI discontinuation, a status termed treatment free remission (TFR). Unfortunately, 5–10% of patients fail TKIs due to resistance and are at risk of progression to BP-CML, which is curable only with hematopoietic stem cell transplantation. Overcoming TKI resistance, improving the prognosis of BP-CML and improving the rates of TFR are areas of active research in CML.
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影响因子：
20.3
作者：
Bumm, T;M端ller, C;Deininger, MWN
通讯作者：
Deininger, MWN
影响因子：
20.3
作者：
Cortes, Jorge;Rousselot, Philippe;Baccarani, Michele
通讯作者：
Baccarani, Michele
影响因子：
10.1
作者：
Carter, Bing Z.;Mak, Po Yee;Andreeff, Michael
通讯作者：
Andreeff, Michael
影响因子：
6.2
作者：
Cortes JE;Kantarjian HM;Rea D;Wetzler M;Lipton JH;Akard L;Khoury HJ;Michallet M;Guerci-Bresler A;Chuah C;Hellmann A;Digumarti R;Parikh PM;Legros L;Warzocha K;Baccarani M;Li E;Munteanu M;Nicolini FE
通讯作者：
Nicolini FE
DOI：
10.1056/nejmoa1306494
发表时间：
2013-11-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cortes JE;Kim DW;Pinilla-Ibarz J;le Coutre P;Paquette R;Chuah C;Nicolini FE;Apperley JF;Khoury HJ;Talpaz M;DiPersio J;DeAngelo DJ;Abruzzese E;Rea D;Baccarani M;Müller MC;Gambacorti-Passerini C;Wong S;Lustgarten S;Rivera VM;Clackson T;Turner CD;Haluska FG;Guilhot F;Deininger MW;Hochhaus A;Hughes T;Goldman JM;Shah NP;Kantarjian H;PACE Investigators
通讯作者：
PACE Investigators