Barlogie B, Stass S, Dixon D, Keating M, Cork A, Trujillo J M, McCredie K B, Freireich E J
Cancer Genet Cytogenet. 1987 Oct;28(2):213-28. doi: 10.1016/0165-4608(87)90207-x.
Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.
我们运用流式细胞术技术，测定了318例新诊断的成年急性白血病患者骨髓中的DNA倍体水平。总体而言，26%的患者表现出DNA干系异常，通常DNA过量10%-15%，与形态学诊断无关。DNA非整倍体在超二倍体染色体数和核型不稳定的患者中最为常见（50%），但在三分之一的染色体易位患者以及20%核型正常的二倍体患者中也存在。因此，在73例DNA非整倍体患者中，近40%的患者观察到了数量上一致的核型异常；其余患者DNA含量与染色体数之间的差异可能分别反映了处于G1/0期或有丝分裂期的靶细胞在细胞周期位置上的差异。细胞遗传学影响急性髓系白血病（AML）的治疗结果，与有数字异常的患者相比，有易位的患者短期和长期预后更有利。在有易位的AML患者中，异常DNA干系的存在确定了一个预后较好的亚组，其缓解期和生存期明显更长（分别为25个月和26个月，而其他患者为18个月和13个月）。此外，AML中DNA非整倍体的预后意义与年龄有关，即有易位的患者中的有利影响以及有数字异常或二倍体核型的患者中的不利影响在年轻患者（小于40岁）中最为明显，而在老年患者（大于或等于40岁）中则不明显。在成人急性淋巴细胞白血病（ALL）中，DNA非整倍体与较短的生存期相关（二倍体组为15个月，而其他组为39个月），这一观察结果与儿童ALL的近期研究结果明显不同。我们的结果表明，DNA流式细胞术对于检测基因组异常是标准细胞遗传学的补充；并且与儿童ALL不同，在成人ALL中未出现，但在一部分成人AML患者中，DNA非整倍体作为一种新的有利预后特征出现，其生物学基础仍有待确定。
