Expression of recombination activating genes-1 and-2 immunoglobulin heavy chain gene rearrangements in acute myeloid leukemia: evaluation of biological and clinical significance in a series of 76 uniformly treated patients and review of the literature.
OBJECTIVE
Early lymphoid differentiation is characterized by antigen receptor gene rearrangements; the rearrangement process is governed by two lymphoid-specific genes, RAG (recombinase activating gene)-1 and -2. The available data on the incidence and prognostic significance of clonal immunoglobulin heavy chain (IgH) gene rearrangements in acute myeloid leukemia (AML) are rather contradictory. The aim of this study was to evaluate the incidence and prognostic significance of RAG-1 and -2 mRNA transcripts and clonal IgH gene rearrangements in a cohort of uniformly treated AML patients; the available literature is also reviewed.


METHODS
The study was performed on 76 AML patients, newly diagnosed between August 1996 and November 1999. RAG-1/-2 gene expression was analyzed by a reverse transcriptase polymerase chain reaction technique and IgH gene rearrangements were detected with variable region (VH) family-specific and consensus framework region (FWR)-2 and/or-3 primers. Statistical associations were explored between IgH monoclonality/ RAG mRNA expression and: (i) age, gender, FAB subtype, immunophenotype, cytogenetic risk groups; (ii) response variables (response/relapse incidence, survival).


RESULTS
In total, 38/75 samples (50.6%) were RAG-1 and/or -2 positive; 30/76 samples (39.5%) carried clonal IgH genes, whereas 13/30 IgH-positive samples (43.3%) were RAG-1/2-negative. Significant associations were detected only for RAG-2 positivity and unfavorable karyotype and IgH monoclonality and FAB subtypes M4/ M5; no association was identified with response outcome and survival.


CONCLUSIONS
Lymphoid-specific molecular markers are detected in a significant proportion of AML patients, regardless of differentiation status (assessed morphologically/ immunophenotypically); however, in our experience, they do not seem to constitute an adverse prognostic factor.
Stavroyianni
Niki
N
P.O. Box 51, 57010 Asvestohori, Thessaloniki, Greece. stavstam@otenet.gr
Belessi
Chrysoula
C
Stamatopoulos
Kostas
K
Kosmas
Christos
C
Paterakis
George
G
Abazis
Danae
D
Pangalos
Constantinos
C
Yataganas
Xenophon
X
D000208:Acute Disease; D015415:Biomarkers; D001853:Bone Marrow; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics*; D016654:Genes, RAG-1 / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064655:V(D)J recombination activating protein 2