Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta.
The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)
Yoneda
N
N
Department of Laboratory Medicine, Kobe University School of Medicine, Japan.
Tatsumi
E
E
Teshigawara
K
K
Nagata
S
S
Nagano
T
T
Kishimoto
Y
Y
Kimura
T
T
Yasunaga
K
K
Yamaguchi
N
N
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015152:Blotting, Northern; D018801:CD2 Antigens; D017252:CD3 Complex / Q000032:analysis* / Q000235:genetics; D018956:CD5 Antigens; D003593:Cytoplasm / Q000737:chemistry; D004254:DNA Nucleotidyltransferases; D005260:Female; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D005838:Genotype; D006651:Histocytochemistry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics; D007945:Leukemia, Lymphoid / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009195:Peroxidase / Q000032:analysis* / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000235:genetics; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D018956:CD5 Antigens; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D009195:Peroxidase; D004254:DNA Nucleotidyltransferases