Expression of human recombinase activating gene 1 and recombinase activating gene 2 [rag 1 and rag 2] in acute lymphoblastic leukemia

ABSTRACT

The process of V[D]J recombination is limited and controlled by the enzymatic activity of cytoplasmic proteins called recombinase which are the products of the activating two genes called Recombinase Activating Gene 1 and Recombinase Activating Gene 2 [RAG1 and RAG 2]. Both genes are expressed in immature B and T lymphocytes and activated V[D]J rearrangement in Ig and TCR genes which are directed in cis by recombination signals sequences [RSSs]. Also, they show variable expression in lymphoid malignancies of both B and T-cell types. This study aimed to focus on the role of the two cytoplasmic proteins [RAG1 and RAG2] in the developing of both B and T ALL, correlation to the stages of differentiation and also, their possible prognostic significance. This study included 40 newly diagnosed acute lymphoblastic leukemic patients [ALL] their age ranged from 1-10 years. Assessment of RAG1 and RAG2 expression by reverse transcriptase polymerase chain reaction [RT-PCR] was done using peripheral blood sample. RAG1 and RAG2 positive expression was higher in frequency in pediatric ALL cases compared to control group, the difference was statistically significant [P<0.01]. Among the RAG1 and RAG2 positive ALL cases 25% were pro-B-ALL and 25% CALL and 31.2% pre-B-ALL and 18.8% were early T-ALL. On the other hand RAG1 and RAG2 negative ALL cases showed higher frequency of CALL phenotype [83.3%] while pro-B ALL, pre-B ALL and early-T ALL were 4.2% and 8.3% and 4.2% respectively. The RAG1 and RAG2 initially positive ALL cases studied had poor prognosis, where 37.5% relapsed and 25%, while 37.5 were in continuous complete remission. However among the RAG1 and RAG2 negative ALL cases studied, 91.7% had good prognosis with complete remission, while only one patient [4.2%] relapsed and one died [4.2%]. A statistical significant association between RAG1 and RAG 2 positive expression and poor prognosis was noticed. RAG1 and RAG2 could be used as prognostic marker in lymphoid malignancies and its sub-classification