Saxena Ankit, Rai Ambak, Raina Vinod, Seth Tulika, Mitra Dipendra Kumar
Cellular Immunology Division, Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Room No. 92, Ansari Nagar, New Delhi, India.
Cancer Immunol Immunother. 2010 Jan;59(1):125-35. doi: 10.1007/s00262-009-0731-6. Epub 2009 Jun 28.
Expression of cell surface CD13 in acute B-cell leukemia (ALL-B) is often viewed, as an aberrant expression of a myeloid lineage marker. Here, we attempted to study the stage specific expression of CD13 on ALL-B blasts and understand its role in leukemogenesis as pertaining to stage of B-cell ontogeny. A total of 355 cases of different hematological malignancies were diagnosed by immunophenotyping. Among 68 cases of early B-cell ALL, 22 cases with distinct immunophenotype was identified as immature B-cell ALL. Blasts from these ALL-B patients demonstrated prominent expression of CD10, CD19, CD22, but neither cytoplasmic nor surface IgM receptors. This strongly indicates leukemogenesis at an early stage of B-cell development. We also identified, the existence of a subpopulation of cells with remarkably similar phenotype in non-leukemic marrow from healthy subjects (expressing CD10, CD19, CD22, CD24, Tdt together with the co-expression of CD13). This sub-population of B cells concomitantly expressing CD13 appeared to be a highly proliferating group. By blocking their cell surface CD13 in leukemic blasts with monoclonal antibody we were able to inhibit their proliferation. We hypothesized that neoplastic transformation at this stage may be facilitated by CD13. CD13 may thus be an important target for novel molecular therapy of early stage acute B-cell leukemia.
急性B淋巴细胞白血病(ALL-B)中细胞表面CD13的表达通常被视为髓系谱系标志物的异常表达。在此,我们试图研究ALL-B原始细胞中CD13的阶段特异性表达,并了解其在白血病发生过程中与B细胞个体发育阶段相关的作用。通过免疫表型分析诊断了总共355例不同的血液系统恶性肿瘤。在68例早期B细胞ALL中,22例具有独特免疫表型的病例被鉴定为不成熟B细胞ALL。这些ALL-B患者的原始细胞表现出CD10、CD19、CD22的显著表达,但既没有细胞质也没有表面IgM受体。这强烈表明白血病发生于B细胞发育的早期阶段。我们还发现在健康受试者的非白血病骨髓中存在一个表型非常相似的细胞亚群(表达CD10、CD19、CD22、CD24、末端脱氧核苷酸转移酶(Tdt)并共表达CD13)。这个共表达CD13的B细胞亚群似乎是一个高度增殖的群体。通过用单克隆抗体阻断白血病原始细胞表面的CD13,我们能够抑制它们的增殖。我们推测在这个阶段肿瘤转化可能由CD13促进。因此,CD13可能是早期急性B淋巴细胞白血病新型分子治疗的一个重要靶点。