Department of Pathology, The University of Texas Medical Center Health Sciences Center, Houston, Texas, USA.
Cancer. 2011 Sep 1;117(17):4009-17. doi: 10.1002/cncr.25978. Epub 2011 Mar 1.
Philadelphia chromosome (Ph)-positive B-lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy.
The authors studied 65 adult patients with Ph-positive acute lymphoblastic leukemia (ALL) who received treatment with TKI-based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with those from 60 adult patients with diploid B-cell ALL who received similar chemotherapy without a TKI.
Ph-positive ALL was associated with older age (P = .01), the common-B immunophenotype characterized by a greater frequency of CD13 (alanine aminopeptidase) coexpression (P = .004), CD66c (carcinoembryonic antigen-related cell adhesion molecule 3) expression (P = .007), and CD25 (interleukin-2 receptor alpha chain) expression (P < .001) and with a lower frequency of CD15 (3-fucosyl-N-acetyl-lactosamine) expression (P < .001). Conventional karyotypic analyses indicated that the Ph chromosome was the sole abnormality in 19 patients (30%), was present with other aberrancies in 43 patients (65%), and was absent (detectable only by fluorescence in situ hybridization [FISH] or quantitative reverse transcriptase-polymerase chain reaction [RT-PCR] analysis) in 3 patients (5%). The presence of the breakpoint cluster region-v-Abelson murine leukemia viral oncogene homolog fusion gene (BCR-ABL) was confirmed in all patients by FISH or RT-PCR (the 190-kDa protein [p190] construct was present in 49 patients [77%], and the p210 fusion transcript construct was present in 15 patients [23%]). The presence of a supernumerary Ph chromosome was correlated with a higher incidence of CD20 (B-lymphocyte antigen, nonglycosylated phosphoprotein) expression (P < .001), whereas the p210 construct was correlated with aberrant CD25 expression (P = .05). Outcomes were not influenced by the degree of karyotypic complexity (including the presence or absence of a supernumerary Ph chromosome), CD20 expression, or myeloid antigen expression (CD13, CD33 [myeloid lineage transmembrane receptor], CD66c). CD25 expression was associated with inferior survival in univariate analysis (P = .051) but not in multivariate analysis (P = .092).
In the context of intensive, TKI-based chemotherapy, the immunophenotypic, karyotypic, and molecular heterogeneity of Ph-positive ALL no longer influences outcome.
费城染色体（Ph）阳性 B 系淋巴母细胞白血病表现出免疫表型、核型和分子遗传学异质性。在基于酪氨酸激酶抑制剂（TKI）的强化化疗背景下，评估了这些参数的预后意义。
作者研究了 65 例接受基于 TKI 的治疗的 Ph 阳性成人急性淋巴细胞白血病（ALL）患者，将其临床病理异质性与患者结局相关联，并将结果与 60 例接受无 TKI 的类似化疗的二倍体 B 细胞 ALL 成人患者进行比较。
Ph 阳性 ALL 与年龄较大有关（P=.01），常见-B 免疫表型特征为 CD13（丙氨酸氨肽酶）共表达频率较高（P=.004），CD66c（癌胚抗原相关细胞粘附分子 3）表达（P=.007）和 CD25（白细胞介素-2 受体α链）表达（P<0.001），CD15（3-岩藻糖-N-乙酰乳糖胺）表达频率较低（P<0.001）。常规核型分析表明，Ph 染色体在 19 例患者（30%）中为唯一异常，在 43 例患者（65%）中与其他异常共存，在 3 例患者（5%）中缺失（仅通过荧光原位杂交[FISH]或实时定量逆转录聚合酶链反应[RT-PCR]分析检测到）。通过 FISH 或 RT-PCR 证实所有患者均存在断点簇区-v-Abelson 鼠白血病病毒致癌基因同源物融合基因（BCR-ABL）（49 例患者[77%]存在 190 kDa 蛋白[p190]构建体，15 例患者[23%]存在 p210 融合转录本构建体）。超数 Ph 染色体的存在与更高的 CD20（B 淋巴细胞抗原，非糖基化磷酸蛋白）表达相关（P<0.001），而 p210 构建体与异常 CD25 表达相关（P=.05）。核型复杂性（包括超数 Ph 染色体的存在与否）、CD20 表达或髓系抗原表达（CD13、CD33[髓系跨膜受体]、CD66c）均不影响结局。单变量分析时 CD25 表达与生存不良相关（P=.051），但多变量分析时无相关性（P=.092）。
在强化、基于 TKI 的化疗背景下，Ph 阳性 ALL 的免疫表型、核型和分子遗传学异质性不再影响结局。
