Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity.
OBJECTIVE
Mixed lineage leukemia (MLL) abnormalities occur in approximately 50% of childhood pro-B acute lymphoblastic leukemia (ALL). However, the incidence and type of MLL rearrangements have not been determined in common ALL (cALL) and CD10+ or CD10- pre-B ALL.


METHODS
To address this question, we analyzed 29 patients with pro-B ALL, 11 patients with CD10- pre-B ALL, 23 pre-B, and 26 cALL patients with CD10 on 20% to 80%, as well as 136 pre-B and 143 cALL patients with CD10 > or = 80% of blasts. They were all enrolled in four Austrian ALL multicenter trials. Conventional cytogenetics were done to detect 11q23 abnormalities and in parallel the potential involvement of the MLL gene was evaluated with a split apart fluorescence in situ hybridization probe set.


RESULTS
We found that 15 of 29 pro-B ALL, 7 of 11 CD10- pre-B ALL, and 1 of 2 French-American-British classification L1 mature B-cell leukemia cases had a MLL rearrangement. However, no 11q23/MLL translocation was identified among the CD10+ pre-B and cALL patients. MLL-rearranged pro-B and CD10- pre-B ALL cases had similar clinical and immunophenotypic (coexpression of CDw65 and CD15) features at initial diagnosis.


CONCLUSIONS
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. However, direct experimental data are needed to confirm this observation.
Attarbaschi
Andishe
A
Department of Hematology and Oncology, St. Anna Children's Hospital, Vienna, Austria.
Mann
Georg
G
König
Margit
M
Steiner
Manuel
M
Strehl
Sabine
S
Schreiberhuber
Anita
A
Schneider
Björn
B
Meyer
Claus
C
Marschalek
Rolf
R
Borkhardt
Arndt
A
Pickl
Winfried F
WF
Lion
Thomas
T
Gadner
Helmut
H
Haas
Oskar A
OA
Dworzak
Michael N
MN
D000293:Adolescent; D001402:B-Lymphocytes; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015260:Neprilysin; D010641:Phenotype; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D007143:Immunoglobulin Heavy Chains; D051788:Myeloid-Lymphoid Leukemia Protein; D015260:Neprilysin