Immunoglobulin and T-cell receptor delta gene rearrangements are rarely found in myelodysplastic syndromes in chronic phase

Abstract

Clonality, in MDS, can only be assessed in patients with chromosomal rearrangements or in females heterozygote for X chromosome restricted polymorphisms. “Illegitimate” rearrangements of the immunoglobulin heavy chain (Ig H) gene and incomplete rearrangements involving Vδ 2 and Dδ 3 segments of the T-cell receptor delta (TcR δ) gene are seen in some cases of AML, and AML post-SMD, and can be detected by a sensitive PCR method. In order to analyse clonality in additional cases in MDS, we looked for Ig H and TCR δ gene rearrangement by PCR in 95 cases of MDS. A rearrangement of the Ig H gene was seen in 2 of the 95 patients: in the circulating blood of 2 of the 36 cases of chronic myelomonocytic leukaemia (CMML) and in none of the marrow samples of the other 59 MDS. A rearrangement of the TcR δ gene (involving Vδ 2 and Dδ 3 segments) was seen in three cases (in the circulating blood of two other CMLL patients, and in the bone marrow of another MDS patient). Twenty-five of the 90 case of MDS with negative PCR findings, in addition to the five cases with positive PCR findings underwent Southern blot analysis of Ig H and TcR δ genes, and PCR analysis of Vδ 1 and Jδ 1 segments of the TcR δ gene. Those examinations were normal in all the cases tested. In patients with positive PCR findings for Ig H or Vδ 2 Dδ 3 rearrangements, the proportion of rearranged cells was evaluated at 1–5% in four cases, and 5–10% in the remaining patient. Because the analysis was performed on total circulating leukocytes or total nucleated marrow cells, the nature of the clonal population in positive cases (lymphoid cells ? myeloid cells ? blasts ?) could not be determined. From a practical point of view, Ig H and TcR δ gene rearrangements seem to very rare in MDS, and cannot be used as clonality markers in most cases.