Coagulation FXIII-A protein expression defines three novel sub-populations in pediatric B-cell progenitor acute lymphoblastic leukemia characterized by distinct gene expression signatures

Leukemic B-cell precursor (BCP) lymphoblasts were recently identified as a novel expression site for coagulation factor XIII subunit A (FXIII-A). The FXIII-A negative subgroup was significantly associated with the ‘B-other’ genetic category and had an unfavorable disease outcome RNA was extracted from bone marrow lymphoblasts of 42 pediatric patients with BCP-acute lymphoblastic leukemia (ALL). FXIII-A expression was determined by multiparameter FC. Genetic diagnosis was based on conventional cytogenetic method and fluorescence in situ hybridization. Affymetrix GeneChip Human Primeview array was used to analyze global expression pattern of 28869 well-annotated genes. Sub-groups were createdtwo way: 1) based on the protein expression of FXIII-A: FXIII-A negative group (<20% FXIII-A positive lymphoblasts), FXIII-A dim group (20%-79% FXIII-A positive lymphoblasts), FXIII-A positive group (≥80% FXIII-A positive lymphoblasts) 2) based on genetic sub-type: non-B-other: - low-risk including t(12;21)/ETV6/RUNX1(TEL-AML1) and high hyperdiploidy (51-65 chromosome), - high-risk including MLL translocations, iAMP21, complex karyotype, near haploidy (chromosome number 23-29), and low hypodiploidy (chromosome<45) - intermediate risk with t(1;19) translocations, B-other: anything else not belonging to the upper categories which are currently genetically unclassified