Protein 4.1 deficiency and deletion of chromosome 20q are associated with acquired elliptocytosis in myelodysplastic syndrome

Abstract

We report a case of myelodysplastic syndrome (MDS), associated with prominent elliptocytosis. A 66-year-old male presented with peripheral pancytopenia, and was diagnosed with MDS [refractory anaemia (RA)]. Apart from marked elliptocytosis, dyshaematopoietic features were not evident in his peripheral blood or hypercellular bone marrow. After 18 months, he had progressed to RA with excess blasts in transformation. Analysis of red blood cell membrane proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a reduced quantity of protein 4.1 (30% of control). Deletion of chromosome 20q was identified by conventional cytogenetic analysis and fluorescence in situ hybridization. Marked elliptocytosis, persistent for more than 17 months, decreased strikingly after chemotherapy with idarubicin and Ara-C. These findings suggest that acquired elliptocytosis occurred as an unusual morphological feature of MDS, associated with abnormalities of protein 4.1 and chromosome 20q.

Association between myeloid malignancies and acquired deficit in protein 4.1R: A retrospective analysis of six patients

“…This chromosomal deletion occurring in an early hematopoietic precursor has drastic consequences on megakaryocytic and erythroblastic differentiation [16]. We found this deletion in four patients over six and two other cases have been reported before [7,10]. Deletion del (20q) could lead to the loss of one gene located in the same area and implicated in the trans-regulation of the EBP41 gene.…”

“…For two of them, elliptocytosis was clearly related to a qualitative or quantitative alteration in protein 4.1R [7,10]. We report here six patients with MDS or CMPD and an acquired deficit in protein 4.1R.…”

“…A few case reports presenting an association between MDS and elliptocytosis have already been presented [5][6][7][8][9][10]. In two cases, elliptocytosis was associated with a qualitative and/ or quantitative alteration in the protein 4.1R [7,10].…”

L’association des neutrophiles hypogranulaires et vacuolisés à l’érythrophagocytose par les neutrophiles est un marqueur utile dans les syndromes myélodysplasiques avec del(20q) ou ider(20q) : une étude multicentrique

“…Comme montré dans le Tableau 2, de l'elliptocytose [36] a été détectée dans seulement 5 % des SMD avec del(20q) et dans 30 % des SMD avec ider(20q). Des elliptocytoses marquées ont été décrites en association avec un SMD dans sept cas dont quatre qui montraient une del(20q) isolée [13,14]. Notre série n'a pas réussi à confirmer l'association entre del(20q) et elliptocytose puisque cette dernière n'est pas restreinte à del(20q) et était présent chez trois patients avec SMD avec une ider(20q) isolée et chez six SMD sans del(20q) ou ider(20q).…”

“…Del(20q) implique préférentiellement les précurseurs érythroïdes et mégacaryocytiques [11] et a été parfois associé avec de l'elliptocytose [13,14].…”