Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases
Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases
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DOI：
10.1182/blood-2008-12-196568
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发表时间：
2009-07-16
期刊：
影响因子：
20.3
通讯作者：
Foa, Robin
中科院分区：
文献类型：
--
作者：
Del Giudice, Ilaria;Chiaretti, Sabina;Foa, Robin
在慢性淋巴细胞白血病（CLL）中，自发性消退是一种特殊现象，其生物学特征尚不清楚。我们描述了9例慢性淋巴细胞白血病患者谁经历了一个自发的临床消退超过11年的随访，尽管残留的肿瘤克隆流式细胞术检测。CD 38和ZAP-70均为阴性。免疫球蛋白重链可变区（IgVH）基因在所有7例可评价患者中均发生突变，其中6例仅限于VH 3家族，2例使用V（H）3-30基因。8例中有6例轻链可变区基因突变，3例使用V（k）4-1基因。CLL细胞的微阵列分析显示了一个独特的基因组图谱，BCR相关基因和核糖体基因，信号转导和转录的调节因子的过度表达。表达IFN-γ、TNF-α和IL-4的活化T淋巴细胞的数量在CLL自发消退和健康人之间相似。总之，尽管肿瘤克隆持续存在，但CLL可发生自发临床消退，生物学特征包括阴性CD 38和ZAP-70，突变的VH 3 -30和V（k）4-1基因。独特的基因谱表明，BCR信号可能在这种情况下发挥重要作用，作为白血病克隆消退的最重要特征。（血。2009; 114：638-646）
In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional phenomenon, whose biologic features are unknown. We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year follow-up, despite a residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of V(H)3-30 gene in 2. The light chain variable region genes were mutated in 6 of 8 cases, with the use of V(k)4-1 gene in 3. Microarray analysis of CLL cells showed a distinctive genomic profile with an overrepresentation of BCR-related and ribosomal genes, regulators of signal transduction and transcription. The number of activated T lymphocytes expressing IFN-gamma, TNF-alpha, and IL-4 was similar between CLL in spontaneous regression and healthy persons. In conclusion, spontaneous clinical regressions can occur in CLL despite the persistence of the neoplastic clone, and the biologic features include negative CD38 and ZAP-70, mutated VH3-30 and V(k)4-1 genes. The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression. (Blood. 2009; 114: 638-646)