Characterization of CD22 expression in acute lymphoblastic leukemia.
BACKGROUND
CD22 is a B-lineage differentiation antigen that has emerged as a leading therapeutic target in acute lymphoblastic leukemia (ALL).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Pediatric Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, Maryland.
Nirali N
NN
Shah
Maryalice Stetler
MS
Stevenson
Constance M
CM
Yuan
Kelly
K
Richards
Cindy
C
Delbrook
Robert J
RJ
Kreitman
Ira
I
Pastan
Alan S
AS
Wayne
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000032:analysis* / Q000037:antagonists & inhibitors
C497867:CD22 protein, human; C497422:KMT2A protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
CD22; acute lymphoblastic leukemia; monoclonal antibody; relapse