PreB1 (CD10^-) Acute Lymphoblastic Leukemia: Immunophenotypic and Genomic Characteristics, Clinical Features and Outcome in 38 Adults and 26 Children

Abstract

The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome

“…In our study, the frequency of pro-B-ALL cases, calculated within the entire ALL population, was 16%. This incidence is slightly superior to the percentage reported in other recent studies on adult ALL, 13,25,26 but it is close to the percentage 13.4% reported in a previous GIMEMA study carried out in 304 adult patients with ALL immunophenotyped in 43 Italian centers between 1988 and 1991. 27 Within B-lineage ALL, the prevalence of pro-B-ALL was 21.4%.…”

High frequency of pro-B acute lymphoblastic leukemia in adults with secondary leukemia with 11q23 abnormalities

“…Prior studies have confirmed the correlation between lack of CD10 expression in ALL with aberrant CD15 and CD65 expression and MLL rearrangements in both adults and infants. [17][18][19][20] Other similarities between infant pro-B ALL and therapy-related leukemia have also been described. Cimino et al 21 analyzed the specific breakpoints in the MLL gene in infant leukemias, de novo leukemias and topoisomerase II inhibitor-related leukemias, and found similarities in gene breakpoints between the infant and therapy-related group that was not found in the de novo leukemia group.…”

Adult acute lymphoblastic leukaemia

“…Immunological markers B-I (pro-B) ALL No further B-cell differentiation marker (only HLA-DR, TdT, CD34) B-II (common) ALL As above, plus CD10 B-III (pre-B) ALL As B-I/B-II, plus cytoplasmic IgM B-IV (mature) ALL Cytoplasmic/surface kappa or lambda Among other markers, stages B-I and B-II are often CD24 positive and 4G7 (pro-and pre-B surrogate light chain specific MoAb) positive [25,26]; surface CD20 and CD22 are variably positive beyond stage B-I; CD13 and CD33 myeloid/cross lineage antigen can be expressed, as well as the CD34 stem-cell antigen, particularly in Ph + ALL (often B-II with CD34, CD38, CD25 and CD13/33) [27,28], but myeloid-specific CD117 should not be present and can be used to differentiate further between ALL and rare myeloid leukemias with negative myeloperoxidase expression (see Section 2.2) [29]. Pro-B ALL with t(4;11)/MLL rearrangements is most often myeloid antigen-positive disease (including expression of CD15).…”