PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROME CAN HAVE POLYCLONAL OR CLONAL HEMATOPOIESIS IN COMPLETE HEMATOLOGICAL REMISSION

The clonality of mature peripheral blood-derived myeloid and lymphoid cells and bone marrow haemopoietic progenitors from 18 Females with my elodysplasia (MDS) (five refractory anaemia, RA; one RA with ringed si deroblasts, RARS; three chronic myelomonocytic leukaemia, CMML; four R A with excess of blasts, RAEB: five RAEB in transformation, RAEB-t) ct as studied by X-chromosome inactivation analysis. Using the human and rogen-receptor (HUMARA) assay we analysed the clonal patterns of highl y purified immature CD34(+)38(-) and committed CD34(+)38(+) marrow-der ived progenitors, and CD16(+)14(-) granulocytes, CD14(+) monocytes, CD 3(+) T and CD19(+) B lymphocytes from peripheral blood. In high-risk p atients (RAEB, RAEB-tl, clonality analysis was performed before and af ter intensive remission-induction treatment, AII patients, except one with RA, had predominance of a single clone in their granulocytes and monocytes. The same clonal pattern was found in CD34(+) progenitor cel ls. In contrast, CD3(+) T lymphocytes were polyclonal or oligoclonal i n 14/18 patients, X-chromosome inactivation patterns of CD19+ B cells were highly concordant with CD3(+) T cells except for two patients ton e RA, one CMML) with monoclonal B and polyclonal T lymphocytes, theref ore suggesting a cIonal mutation in a progenitor common to the myeloid and B-lymphoid lineages or the coexistence of MDS and a B-cell disord er in these particular patients. After high-dose non-myeloablative che motherapy, polyclonal haemopoiesis was reinstalled in the mature myelo id cells and immature and committed marrow progenitors in three of fou r patients achieving complete haematological remission. Therefore we c onclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis.