PAX5 expression in acute leukemias: higher B-lineage specificity than CD79a and selective association with t(8;21)-acute myelogenous leukemia.
The transcription factor PAX5 plays a key role in the commitment of hematopoietic precursors to the B-cell lineage, but its expression in acute leukemias has not been thoroughly investigated. Hereby, we analyzed routine biopsies from 360 acute leukemias of lymphoid (ALLs) and myeloid (AMLs) origin with a specific anti-PAX5 monoclonal antibody. Blasts from 150 B-cell ALLs showed strong PAX5 nuclear expression, paralleling that of CD79a in the cytoplasm. Conversely, PAX5 was not detected in 50 T-cell ALLs, including 20 cases aberrantly coexpressing CD79a. Among 160 cytogenetically/molecularly characterized AMLs, PAX5 was selectively detected in 15 of 42 cases bearing the t(8;21)/AML1-ETO rearrangement. Real-time reverse transcription-PCR studies in t(8;21)-AML showed a similar up-regulation of PAX5 transcript in all of the 8 tested samples (including 4 cases that were negative at anti-PAX5 immunostaining), suggesting that PAX5 is expressed in t(8;21)-AML more widely than shown by immunohistochemistry. Interestingly, PAX5(+) t(8;21)-AML also expressed CD79a and/or CD19 (major transcriptional targets of PAX5 in B-cells) in 10 of 12 evaluable cases. Our results indicate that PAX5 is a more specific marker than CD79a for B-cell ALL diagnosis. Moreover, among AMLs, PAX5 expression selectively clusters with t(8;21), allowing its immunohistochemical recognition in a proportion of cases, and likely explaining a peculiar biological feature of this subset of myeloid leukemias, i.e. the aberrant expression of B-cell genes.
Tiacci
Enrico
E
Institutes of Hematology and Internal Medicine, University of Perugia, Perugia, Italy.
Pileri
Stefano
S
Orleth
Annette
A
Pacini
Roberta
R
Tabarrini
Alessia
A
Frenguelli
Federica
F
Liso
Arcangelo
A
Diverio
Daniela
D
Lo-Coco
Francesco
F
Falini
Brunangelo
B
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis*; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051925:CD79 Antigens; D045744:Cell Line, Tumor; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051757:PAX5 Transcription Factor; D000075142:RUNX1 Translocation Partner 1 Protein; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014178:Translocation, Genetic
C107844:AML1-ETO fusion protein, human; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D051925:CD79 Antigens; C497881:CD79A protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D000075142:RUNX1 Translocation Partner 1 Protein; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors