The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, John Hopkins University, Baltimore, MD, USA.
Leuk Lymphoma. 2022 Jul;63(7):1617-1623. doi: 10.1080/10428194.2022.2038375. Epub 2022 Mar 27.
The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Immunoglobulin heavy chain variable region (IgHV) mutation status is among the most important prognostic factors, with unmutated IgHV associated with inferior outcomes. CLL presumably arises from mature B cells. However, we hypothesized that IgHV unmutated CLL could arise early in B cell differentiation. We prospectively studied 29 patients with mutated and 88 with unmutated IgHV CLL for the presence of CD34CD19 cells harboring CLL chromosomal abnormalities. CD34CD19 cells were never detected in mutated CLL. In contrast, a small but distinct population of CD34CD19 cells harboring the CLL chromosomal abnormality was present in 86/88 patients with unmutated IgHV across all cytogenetic subtypes. Moreover, the CD34CD19 cells generated a 3.8 ± 0.7 fold CLL cell expansion over 3-4 weeks in cultures containing IL-3 and IL-2. Unmutated IgHV CLL appears to arise in CD34 B cells, which perhaps contributes to its poorer prognosis.
慢性淋巴细胞白血病 (CLL) 的临床病程变化多样。免疫球蛋白重链可变区 (IgHV) 突变状态是最重要的预后因素之一，未突变的 IgHV 与较差的预后相关。CLL 可能起源于成熟 B 细胞。然而，我们假设 IgHV 未突变的 CLL 可能在 B 细胞分化的早期出现。我们前瞻性地研究了 29 例突变型和 88 例未突变型 IgHV CLL 患者，以检测是否存在携带 CLL 染色体异常的 CD34CD19 细胞。在突变型 CLL 中从未检测到 CD34CD19 细胞。相比之下，在所有细胞遗传学亚型的 88 例未突变 IgHV 患者中，均存在一小部分但明显的 CD34CD19 细胞群，携带 CLL 染色体异常。此外，在含有 IL-3 和 IL-2 的培养物中，CD34CD19 细胞在 3-4 周内产生了 3.8±0.7 倍的 CLL 细胞扩增。未突变的 IgHV CLL 似乎起源于 CD34 B 细胞，这可能导致其预后较差。
