Approximately half of patients with chronic myeloid leukemia (CML) in sustained deep molecular response who discontinue tyrosine kinase inhibitors (TKIs) remain in treatment-free remission (TFR). Some of these patients have measurable residual disease (MRD) by BCR-ABL1 mRNA testing, and most have detectable BCR-ABL1 DNA by highly sensitive methods. We used fluorescence-activated cell sorting and BCR-ABL1 DNA PCR to investigate the lineage of residual CML cells in TFR. Twenty patients in TFR for >1 year provided blood for sorting into granulocytes, monocytes, B cells, T cells, and NK cells. MRD was identified predominantly in the lymphoid compartment and never in granulocytes. B cells were more often BCR-ABL1 positive than T cells (18 vs 11/20 patients) and at higher levels (median 10^−4.9 vs 10^−5.7; P = 0.014). In 13 CML patients studied at diagnosis lymphocytes expressing BCR-ABL1 mRNA comprised a small proportion of total leukocytes. These data improve our understanding of TFR biology, since it is now clear that MRD in the blood of TFR patients need not imply the persistence of multipotent CML cells. Lineage-specific assessment of MRD could be explored as a means to improve the prediction of TFR.

持续约有深度分子反应的慢性髓样白血病（CML）患者中，约有一半的停用酪氨酸激酶抑制剂（TKIs）的患者仍处于无治疗缓解期（TFR）。这些患者中有一些通过BCR-ABL1 mRNA检测具有可测量的残留疾病（MRD），而大多数患者通过高度敏感的方法具有可检测的BCR-ABL1 DNA。我们使用荧光激活细胞分选和BCR-ABL1 DNA PCR来研究TFR中残余CML细胞的谱系。TFR超过20年的20名患者提供了血液以分选为粒细胞，单核细胞，B细胞，T细胞和NK细胞。MRD主要在淋巴区室中发现，从未在粒细胞中发现。B细胞更多是BCR-ABL1与T细胞相比阳性（18例与11/20例），且水平更高（中位数10 ^－4.9对10 ^－5.7；P  = 0.014）。在诊断中研究的13名CML患者中，表达BCR-ABL1 mRNA的淋巴细胞占总白细胞的一小部分。这些数据改善了我们对TFR生物学的理解，因为现在很明显，TFR患者血液中的MRD不必暗示多能CML细胞的持久性。可以探索针对MRD的血统特定评估，作为改善TFR预测的一种方法。