T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by increased proliferation and incomplete maturation of T-cell progenitors, for which relapse is often of poor prognosis. To improve patient outcomes, it is critical to understand the chemoresistance mechanisms arising from cell plasticity induced by the bone marrow (BM) microenvironment. Single-cell RNA sequencing of human T-ALL cells from adipocyte-rich and adipocyte-poor BM revealed a distinct leukemic cell population defined by quiescence and high CD44 expression (Ki67^neg/lowCD44^high). During in vivo treatment, these cells evaded chemotherapy, and were further called Chemotherapy-resistant Leukemic Cells (CLCs). Patient sample analysis revealed Ki67^neg/lowCD44^high CLCs at diagnosis and during relapse, with each displaying a specific transcriptomic signature. Interestingly, CD44^high expression in T-ALL Ki67^neg/low CLCs was associated with E-selectin binding. Analysis of 39 human T-ALL samples revealed significantly enhanced E-selectin binding activity in relapse/refractory samples compared with drug-sensitive samples. These characteristics of chemoresistant T-ALL CLCs provide key insights for prognostic stratification and novel therapeutic options.

T 细胞急性淋巴细胞白血病 （T-ALL） 是一种造血系统恶性肿瘤，其特征是 T 细胞祖细胞增殖增加和不完全成熟，其复发通常预后不良。为了改善患者的预后，了解骨髓 （BM） 微环境诱导的细胞可塑性引起的化疗耐药机制至关重要。对来自富含脂肪细胞和缺乏脂肪细胞的 BM 的人 T-ALL 细胞进行单细胞 RNA 测序，揭示了一个独特的白血病细胞群，其特征是静止和高 CD44 表达 （Ki67^neg/lowCD44^high）。在体内治疗期间，这些细胞逃避了化疗，并被进一步称为化疗耐药白血病细胞 （CLC）。患者样本分析显示，诊断和复发时 Ki67^阴性/低CD44^高 CLC，每个 CLC 都显示出特异性转录组特征。有趣的是，CD44 在 T-ALL Ki67^neg/low CLCs 中的^高表达与 E-选择素结合有关。对 39 例人类 T-ALL 样品的分析显示，与药物敏感样品相比，复发/难治性样品中的 E-选择素结合活性显著增强。化疗耐药 T-ALL CLC 的这些特性为预后分层和新的治疗选择提供了关键见解。