Stark B, Jeison M, Gobuzov R, Krug H, Glaser-Gabay L, Luria D, El-Hasid R, Harush M B, Avrahami G, Fisher S, Stein J, Zaizov R, Yaniv I
Cancer Cytogenetic Laboratory, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
Cancer Genet Cytogenet. 2001 Jul 15;128(2):108-13. doi: 10.1016/s0165-4608(01)00411-3.
Near-haploid (<30 chromosomes) acute lymphoblastic leukemia (ALL) is a rare and unique subgroup of childhood common ALL associated with a very poor outcome. It may be underdiagnosed when masked by a co-existing hyperdiploid line, which has to be distinguished from the common good-prognostic hyperdiploid (>50 chromosomes) ALL. We present three children in whom, by conventional cytogenetics, near-haploid ALL was detected on relapse. Using interphase FISH probes of chromosomes X, Y, 4, 12, and 21, we were able, in two cases, to trace the hidden near-haploid lines of approximately 5% and 20% of the cells, masked by hyperdiploid cells of approximately 80% and 70%, respectively; at relapse, the proportion was reversed, with predominant near-haploid lines of over 80% and residual hyperdiploidy of less than 10%. The near-haploid lines consisted of 24 and 27 chromosomes, and always retained the second copy of chromosome 21 or its derivative, as detected in one of our patients by SKY. The hyperdiploid clones were the exact duplicates of the near-haploid ones and contained four and two copies of the chromosomes represented in two and one copies in the near-haploid stem line, respectively. Unlike the common hyperdiploid ALL, no trisomies were observed. The patients were all aged >10 years, with WBC 0.7-30 x 10(9)/L, and a common ALL phenotype. They were treated with the ALL-BFM-95 protocol, medium risk group, and responded well to 8 days of steroid therapy, but relapsed early, within 11 months, and died a few months later. Interphase FISH technique is recommended for the detection of cryptic near-haploid clones in the diagnostic survey of ALL. To assess the prognostic value of near-haploidy in the context of the ALL-BFM protocols, a larger cohort of patients is required.
近单倍体（<30条染色体）急性淋巴细胞白血病（ALL）是儿童常见ALL中一种罕见且独特的亚组，预后很差。当被共存的超二倍体系掩盖时可能会漏诊，必须将其与常见的预后良好的超二倍体（>50条染色体）ALL区分开来。我们报告了3例儿童患者，通过传统细胞遗传学方法在复发时检测到近单倍体ALL。使用染色体X、Y、4、12和21的间期荧光原位杂交（FISH）探针，我们在2例患者中能够追踪到分别被约80%和70%的超二倍体细胞掩盖的约5%和20%细胞的隐藏近单倍体系；复发时，比例发生逆转，近单倍体系占主导，超过80%，残留超二倍体小于10%。近单倍体系由24条和27条染色体组成，并且总是保留21号染色体的第二个拷贝或其衍生物，如我们其中1例患者通过光谱核型分析（SKY）所检测到的。超二倍体克隆是近单倍体克隆的精确复制品，分别包含近单倍体主干系中以2份和1份形式存在的染色体的4份和2份拷贝。与常见的超二倍体ALL不同，未观察到三体现象。这些患者均年龄>10岁，白细胞计数为0.7 - 30×10⁹/L，具有常见ALL表型。他们接受了ALL - BFM - 95方案中风险组的治疗，对8天的类固醇治疗反应良好，但在11个月内早期复发，几个月后死亡。建议在ALL诊断检查中使用间期FISH技术检测隐匿的近单倍体克隆。为了评估在ALL - BFM方案背景下近单倍体状态的预后价值，需要更大规模的患者队列。
