Has Ph-like ALL Superseded Ph+ ALL as the Least Favorable Subtype?
Has Ph-like ALL Superseded Ph+ ALL as the Least Favorable Subtype?
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DOI：
10.1016/j.beha.2021.101331
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Tasian SK
中科院分区：
文献类型：
--
作者：
Tran TH;Tasian SK
费城染色体样急性淋巴细胞白血病（Ph 样 ALL）是高危 B-ALL 的一个子集，在儿童到成人年龄段中与高复发风险和较差的临床结果相关。 Ph 样 ALL 的特征是频繁的 IKZF1 改变和激酶激活的基因表达谱，与费城染色体阳性 (Ph+) ALL 相似，但缺乏典型的 BCR-ABL1 重排。过去十年中高通量测序技术的进步揭示了 Ph 样 ALL 的基因组图谱，揭示了多种激酶激活易位和突变，这些易位和突变可能适合靶向治疗，为 Ph+ ALL 患者树立了卓越的精准医疗范例。过去十年中，为识别和描述 Ph 样 ALL 的合作科学努力直接为当前的精准医学试验提供了信息，这些试验研究基于酪氨酸激酶抑制剂的疗法对患有 Ph 样 ALL 的儿童、青少年和成人的治疗潜力，尽管针对这一高危患者群体的最佳治疗模式尚未建立。在此，我们描述了 Ph 样 ALL 的流行病学、临床特征和生物学，强调了在临床中实施实用且具有成本效益的诊断算法所面临的挑战，并描述了正在积极研究的治疗策略的环境，这些策略致力于降低 Ph 样 ALL 患者的复发风险并提高长期生存率，就像 Ph+ ALL 患者已成功实现的那样。
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subset of high-risk B-ALL associated with high relapse risk and inferior clinical outcomes across the pediatric-to-adult age spectrum. Ph-like ALL is characterized by frequent IKZF1 alterations and a kinase-activated gene expression profile similar to that of Philadelphia chromosome-positive (Ph+) ALL, yet lacks the canonical BCR-ABL1 rearrangement. Advances in high-throughput sequencing technologies during the past decade have unraveled the genomic landscape of Ph-like ALL, revealing a diverse array of kinase-activating translocations and mutations that may be amenable to targeted therapies that have set a remarkable precision medicine paradigm for patients with Ph+ ALL. Collaborative scientific efforts to identify and characterise Ph-like ALL during the past decade has directly informed current precision medicine trials investigating the therapeutic potential of tyrosine kinase inhibitor-based therapies for children, adolescents, and adults with Ph-like ALL, although the most optimal treatment paradigm for this high-risk group of patients has yet to be established. Herein, we describe the epidemiology, clinical features, and biology of Ph-like ALL, highlight challenges in implementing pragmatic and cost-effective diagnostic algorithms in the clinic, and describe the milieu of treatment strategies under active investigation that strive to decrease relapse risk and improve long-term survival for patients with Ph-like ALL as has been successfully achieved for those with Ph+ ALL.
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影响因子：
51.1
作者：
Den Boer, Monique L.;van Slegtenhorst, Marjon;De Menezes, Renee X.;Cheok, Meyling H.;Buijs-Gladdines, Jessica G. C. A. M.;Peters, Susan T. C. J. M.;Van Zutven, Laura C. M.;Beverloo, H. Berna;Van der Spek, Peter J.;Escherich, Gaby;Horstmann, Martin A.;Janka-Schoub, Gritta E.;Kamps, Willem A.;Evans, William E.;Pieters, Rob
通讯作者：
Pieters, Rob
影响因子：
11.4
作者：
Bhojwani D;Sposto R;Shah NN;Rodriguez V;Yuan C;Stetler-Stevenson M;O'Brien MM;McNeer JL;Quereshi A;Cabannes A;Schlegel P;Rossig C;Dalla-Pozza L;August K;Alexander S;Bourquin JP;Zwaan M;Raetz EA;Loh ML;Rheingold SR
通讯作者：
Rheingold SR
影响因子：
4.1
作者：
Chang, Fengqi;Lin, Fumin;Li, Marilyn M.
通讯作者：
Li, Marilyn M.
影响因子：
7.5
作者：
Harvey, Richard C.;Tasian, Sarah K.
通讯作者：
Tasian, Sarah K.
影响因子：
2.7
作者：
Assi, Rita;Kantarjian, Hagop;Jabbour, Elias
通讯作者：
Jabbour, Elias