Shah Nirali N, Stevenson Maryalice Stetler, Yuan Constance M, Richards Kelly, Delbrook Cindy, Kreitman Robert J, Pastan Ira, Wayne Alan S
Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, Maryland.
Pediatr Blood Cancer. 2015 Jun;62(6):964-9. doi: 10.1002/pbc.25410. Epub 2015 Mar 1.
CD22 is a B-lineage differentiation antigen that has emerged as a leading therapeutic target in acute lymphoblastic leukemia (ALL).
Properties of CD22 expression relevant to therapeutic targeting were characterized in primary samples obtained from children and young adults with relapsed and chemotherapy refractory B-precursor (pre-B) ALL.
CD22 expression was demonstrated in all subjects (n = 163) with detection on at least 90% of blasts in 155 cases. Median antigen site density of surface CD22 was 3,470 sites/cell (range 349-19,653, n = 160). Blasts from patients with known 11q23 (MLL) rearrangement had lower site density (median 1,590 sites/cell, range 349-3,624, n = 20 versus 3,853 sites/cell, range 451-19,653, n = 140; P = <0.0001) and 6 of 21 cases had sub-populations of blasts lacking CD22 expression (22%-82% CD22 +). CD22 expression was maintained in serial studies of 73 subjects, including those treated with anti-CD22 targeted therapy. The levels of soluble CD22 in blood and marrow by ELISA were low and not expected to influence the pharmacokinetics of anti-CD22 directed agents.
These characteristics make CD22 an excellent potential therapeutic target in patients with relapsed and chemotherapy-refractory ALL, although cases with MLL rearrangement require close study to exclude the presence of a CD22-negative blast population.
CD22是一种B细胞系分化抗原,已成为急性淋巴细胞白血病(ALL)的主要治疗靶点。
在从复发和化疗难治性B前体(前B)ALL的儿童和年轻成人获得的原代样本中,对与治疗靶向相关的CD22表达特性进行了表征。
在所有受试者(n = 163)中均检测到CD22表达,155例中至少90%的原始细胞可检测到该表达。表面CD22的中位抗原位点密度为3470个位点/细胞(范围349 - 19653,n = 160)。已知有11q23(MLL)重排的患者的原始细胞具有较低的位点密度(中位1590个位点/细胞,范围349 - 3624,n = 20,而3853个位点/细胞,范围451 - 19653,n = 140;P = <0.0001),21例中有6例存在缺乏CD22表达的原始细胞亚群(22% - 82% CD22 +)。在对73名受试者的系列研究中,包括接受抗CD22靶向治疗的受试者,CD22表达得以维持。通过ELISA检测,血液和骨髓中可溶性CD22的水平较低,预计不会影响抗CD22导向药物的药代动力学。
这些特性使CD22成为复发和化疗难治性ALL患者的一个极好的潜在治疗靶点,尽管MLL重排的病例需要密切研究以排除存在CD22阴性原始细胞群体的情况。