Clin Lab. 2024 Sep 1;70(9). doi: 10.7754/Clin.Lab.2024.240323.
Chronic myeloid leukemia (CML), a myeloproliferative neoplasm defined by the BCR::ABL1 fusion gene arising from the Philadelphia chromosome (Ph) translocation t(9:22)(q34;q11), exhibits diverse clinical courses often influenced by additional chromosomal aberrations (ACAs). This report presents a case of CML har-boring a novel four-way Ph translocation involving the X chromosome, offering insights into the interplay between complex karyotypes and treatment response and emphasizing the need for further research into the role of ACAs in CML management.
A 42-year-old man diagnosed with CML in the accelerated phase presented a novel four-way Ph translocation involving chromosomes X, 5, 9, and 22: 46,Y,t(X;5;9;22)(q26;q15;q34;q11.2). Despite achieving a major molecular response initially with imatinib and nilotinib, BCR::ABL1 levels (international scale) increased up to 24.0%, which prompted the use of second-line nilotinib.
Follow-up bone marrow (BM) studies revealed clonal evolution with trisomy 8 and an unclassified ABL1 mutation (E292V), potentially contributing to resistance. Though a transient major molecular response (MMR) occurred after a switch to third-line dasatinib, this change failed to achieve a deep molecular response, and BCR-ABL1 levels were elevated above the MMR.
This case highlights the challenge of ACAs impacting CML treatment response and prognosis. Limited knowledge exists on complex Ph translocations involving the X chromosome, but this report contributes data for further research. Understanding ACA effects on therapeutic response and prognosis requires a detailed study of such complex chromosomal aberrations.
慢性髓性白血病（CML）是一种由费城染色体（Ph）易位 t（9：22）（q34；q11）产生的 BCR::ABL1 融合基因定义的骨髓增生性肿瘤，表现出不同的临床过程，通常受其他染色体异常（ACAs）影响。本报告介绍了一例 CML 伴有新型四向 Ph 易位，涉及 X 染色体，深入了解复杂核型与治疗反应之间的相互作用，并强调需要进一步研究 ACAs 在 CML 管理中的作用。
一名 42 岁男性，诊断为加速期 CML，表现为新型四向 Ph 易位，涉及染色体 X、5、9 和 22：46，Y，t（X；5；9；22）（q26；q15；q34；q11.2）。尽管最初用伊马替尼和尼洛替尼达到主要分子反应，但 BCR::ABL1 水平（国际标准）增加到 24.0%，这促使使用二线尼洛替尼。
后续骨髓（BM）研究显示克隆进化伴有 8 三体和未分类的 ABL1 突变（E292V），可能导致耐药。尽管切换到三线达沙替尼后出现短暂的主要分子反应（MMR），但这种变化未能达到深分子反应，BCR-ABL1 水平高于 MMR。
本病例突出了 ACAs 影响 CML 治疗反应和预后的挑战。关于涉及 X 染色体的复杂 Ph 易位，知识有限，但本报告为进一步研究提供了数据。了解 ACA 对治疗反应和预后的影响需要对这种复杂的染色体异常进行详细研究。
