Studies here respond to two long-standing questions: Are human "pre/pro-B" CD34(+)CD10(-)CD19(+) and "common lymphoid progenitor (CLP)/early-B" CD34(+)CD10(+)CD19(-) alternate precursors to "pro-B" CD34(+)CD19(+)CD10(+) cells, and do the pro-B cells that arise from these progenitors belong to the same or distinct B-cell development pathways?
Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study.
The striking similarities between the two CD10- ALL subsets imply that CD10- pre-B ALL variants may represent pro-B ALL cases that maintained the propensity to rearrange and express their immunoglobulin heavy chain rather than actual pre-B ALL forms transformed at this later stage of B-cell differentiation.
Our data identify CD10- cytoplasmic immunoglobulin-positive pre-B ALL as a rare (2.2%) but distinct immuno-subtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.
All t-ALL cases had a pro-B (CD10-negative) immunophenotype with significantly higher expression of CD15 and CD65, compared to the de novo CD10-positive ALL cases.
To elucidate the biologic and clinical heterogeneity of adult pro-B acute lymphoblastic leukemia (ALL) (ie, terminal deoxynucletidyl-transferase-positive[TdT+], CD19+, CD10-, surface immunoglobulin-negative [SIg-]), we evaluated 66 patients enrolled in the Italian multicentric Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 study between October 1996 and December 1999.
In this prospective study, samples from 478 patients with CD10(+) B-cell precursor ALL (c-ALL and pre-B ALL) underwent BCR-ABL reverse transcription-polymerase chain reaction (RT-PCR) analysis with double testing of positive samples.
The predominant expression of Ik-6, which is the result of post-transcription dysregulation, is characteristic of adult pre-B ALL, especially CD10(+) pre-B ALL.
In contrast to pro-B leukemia cells, pre-pre-B leukemia cells from children with CD19(+)CD10(+) common B-lineage ALL and EBV-transformed B-cell lines from healthy volunteers expressed wild-type Syk coding sequences.
None of the CD34(+)Lin(-) hematopoietic stem cell progenitors or the CD34(+)CD19(+) (pro-B) or the CD19(+)CD10(+) (pre-B/immature B cells) B-cell progenitors expressed CCR6.
Chromosomal translocation was identified in 24 (36.4%) of the ALL patients, 17 of whom had recurrent translocations including 10 with CD10+ B-precursor ALL [4 with t(9;22), 5 with t(1;19), and 1 infant with t(8;14)(q24;q11)], one neonate with CD10- early pre-B ALL with t(4;11), three B-cell cases with t(8;14), and three T-cell cases [2 with t(11;19)(q23;p13), and 1 (11;14)(p13;q11)].One B-precursor patient had dic (9;12).
Our results show that the t(12;21)(p13;q22)+ ALLs display a higher intensity of CD10 (P = 0.0016) and HLADR (P = 0.005) expression together with lower levels of the CD20 (P = 0.01), CD45 (P = 0.01), CD135 (P = 0.003) and CD34 (P = 0.03) antigens as compared to the t(12;21) cases.
We conclude that several of the clinical and laboratory prognostic factors, which are used reliably for B-precursor ALL, are much less predictive in T-ALL (ie age, WBC, consensus risk group, hyperdiploidy, presence of trans- locations and CALLA expression).
In contrast to childhood acute lymphoblastic leukemia (ALL), the cell-biological features, clinical characteristics, and treatment outcome of CD10(-) pro-B ALL have not yet been determined in larger series of adult patients.
Of BCR/ABL-positive patients, 83% had early pre-B ALL, one patient had pre-T ALL, while half of the BCR/ABL-negative patients had early pre-B ALL, 18% had CD10-negative pro-B ALL and 21% were pre-T.