Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B cells

Abstract

Deletions of the long arm of chromosome 20 are associated with several myeloid malignancies and, in particular, with myeloproliferative disorders and myelodysplastic syndromes (MDS). Together with deletions of chromosome 5q and chromosome 7q, chromosome 20q deletions have previously been thought to be restricted to myeloid cells in patients with MDS. We report here that deletion of chromosome 20q in MDS can arise in a multipotent precursor of both myeloid cells and B cells. Clonal Epstein-Barr virus (EBV)-transformed cell lines, both with and without a 20q deletion, have been isolated from a patient with MDS. Moreover, these cell lines have been shown to provide a useful physical mapping tool and have been used to confirm the interstitial nature of the 20q deletion. Microsatellite polymerase chain reaction (PCR) and PCR analysis of PGK gene methylation have been used to study highly purified populations of peripheral blood cells. The 20q deletion was detectable by microsatellite PCR in peripheral blood granulocytes and monocytes but not in B cells or T cells. Clonality of the different lineages followed the same pattern as the 20q deletion. This represents the first report in which a chromosome abnormality associated with MDS has been immortalized in an EBV-transformed lymphoblastoid cell line. Furthermore, our data show that patients with apparent myeloid restriction of a chromosome deletion may in fact have a disease arising in a multipotent cell with both myeloid and lymphoid potential.

Patients with high‐risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission

“…The XCI patterns of CD19 þ B cells were similar to T cells except in two patients (one RA, one CMML) with monoclonal B and polyclonal T lymphopoiesis. This suggests clonal involvement of an MDS progenitor cell common to the myeloid and B-lymphocytic lineages, a finding that has been previously reported to occur in MDS (Raskind et al, 1984;Lawrence et al, 1987;White et al, 1994;Van Lom et al, 1995). Since there is growing evidence that there is an increased association between MDS and lymphoid malignancies (Copplestone et al, 1986;Mitterbauer et al, 1997), our clonality results can also be explained by the concomitant occurrence of MDS and another clonal B-cell disorder.…”

Myelodysplastic Syndrome of del 20q with Plasma Cell Dysplasia

“…16 On the other hand, in vitro, both anti-CD38-and del 20q-positive cells were observed in the Epstein-Barr virus-transformed lymphoid cell line from the cells of a del 20q-MDS case. 17 These reports might indicate that the del 20q-associated cytogenic finding is associated with a chromosomal abnormality related to not only myeloid but also other lineages. Alternatively, MDS with Bcell abnormality might be related to a viral infection such as Epstein-Barr virus.…”

Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice.

“…Interestingly, a deletion of human chromosome 20q involving the region in which the C/EBP[3 gene maps has been reported in several cases of myeloproliferative disorders and myelodisplastic syndromes (14), and in 16 out of 68 patients (24%) affected by myeloid leukemia (15). It has also been shown that such a deletion in myelodysplasia can arise in a multipotent precursor of both myeloid and B cells, suggesting that this mutation can cause a disease arising in a cell with both myeloid and lymphoid potential (16). These reports together with our observation of abnormal proliferation in both myeloid and B cell compartments in C/EBP[3-/-mice, suggest that inactivation of the C/EBP[3 gene could represent a link between myelo-and lympho-proliferative disorders.…”