Myelodysplastic syndromes: A study of surface markers and in vitro growth patterns

Abstract

A study of surface markers and in vitro growth in semi-solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony-forming cells were assessed by culture in semi-solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB-t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS.

Megakaryocyte, Erythroid and Granulocyte-Macrophage Colony Formation in Myelodysplastic Syndromes

“…Three reports pointed out a correlation between colony formation and specific chro mosome abnormalities [8,9,25], while two other reports did not find any relationship between these two param eters [13,26]. Our present study did not reveal any correla tion between colony formation by the three cell lines and the abnormal karyotype.…”

Apparent expansion of CD34+ cells during the evolution of myelodysplastic syndromes to acute myeloid leukemia

“…12, 29,32,47,48 Within AML after MDS the prognostic relevance of CD34 expression has not been demonstrated yet, because no studies on this selected subgroup within AML have been performed. In this study we found a higher CD34 expression in AML after previous MDS as compared with the MDS subgroups, which is the first evidence in literature of a prognostic meaning of CD34 expression in AML-MDS.…”

“…[32][33][34] No clear reports can be found investigating the increased autonomic proliferation in MDS. In RAEB(t) and sAML we previously showed less overall apoptosis, especially in blasts, by using ISEL on BM biopsies.…”

“…38,39 The MDS CD34 + cells show clearly promoted proliferative capacity (high cluster/colony ratio in semi-solid medium) with strongly impaired differentiation upon growth factors in in vitro cultures. [32][33][34] TNF␣ is one of the cytokines which may have a dual role in this process: stimulation of proliferation of presumably early progenitor cells and induction of apoptosis in their more mature progeny. 9,14,20,40,41 29,32 The number of CD34 + aggregates in MDS biopsies are significantly positively correlated with the percentage of BM blasts and ALIPs.…”

“…[32][33][34] TNF␣ is one of the cytokines which may have a dual role in this process: stimulation of proliferation of presumably early progenitor cells and induction of apoptosis in their more mature progeny. 9,14,20,40,41 29,32 The number of CD34 + aggregates in MDS biopsies are significantly positively correlated with the percentage of BM blasts and ALIPs. 45 A significantly higher frequency of CD34 expression is also found in sAML (or therapyrelated AML) when compared with de novo AML.…”