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rHuEpo administration in patients with low‐risk myelodysplastic syndromes: evaluation of erythroid precursors' response by fluorescence in situ hybridization on May–Grunwald–Giemsa‐stained bone marrow samples
Author(s) -
Rigolin Gian Matteo,
Porta Matteo Della,
Bigoni Renato,
Cavazzini Francesco,
Ciccone Maria,
Bardi Antonella,
Cuneo Antonio,
Castoldi Gianluigi
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03867.x
Subject(s) - fluorescence in situ hybridization , myelodysplastic syndromes , bone marrow , erythropoietin , medicine , gastroenterology , pathology , clone (java method) , erythropoiesis , myeloid , anemia , immunology , biology , chromosome , gene , genetics
Summary. The issue of whether, in patients affected by myelodysplastic syndromes (MDS), haematological response to cytokines, particularly to recombinant human erythropoietin (rHuEpo), is a phenomenon related to the stimulation of normal haemopoietic cells or to the differentiation of cells belonging to the abnormal clone remains an open question. To assess the pattern of response to rHuEpo treatment of bone marrow (BM) cells, we evaluated in 13 low‐risk MDS patients with known cytogenetic abnormalities the number of cytogenetically normal and abnormal cells by conventional cytogenetic analysis (CCA) and by a fluorescence in situ hybridization (FISH) technique, enabling the simultaneous visualization of FISH chromosomal abnormalities in morphologically and immunophenotypically identifiable BM elements. Patients responding to rHuEpo presented a lower number of abnormal metaphases at diagnosis in comparison with patients who did not respond (22·74% vs 76·23%, P = < 0·001). This was confirmed by the combined morphological FISH analysis, showing that, before treatment, BM samples from patients responding to rHuEpo had a lower proportion of both FISH abnormal erythroid (36·48% vs 66·93%, P = 0·002) and myeloid (40·76% vs 67·70%, P = 0·014) elements than unresponsive patients. After rHuEpo treatment, responding patients presented a significantly lower proportion of FISH abnormal erythroid precursors than observed before treatment (16·93% vs 36·48%, P = 0·017). Likewise, in responding patients, a significantly lower proportion of FISH abnormal erythroid elements (16·93% vs 66·30%, P < 0·001) was detected in comparison with unresponsive patients. These findings provide evidence that, in low‐risk MDS patients with known cytogenetic abnormalities, response to rHuEpo may be due to the proliferation of karyotypically normal erythroid precursors, possibly representing residual normal erythroid elements.

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