Most common abnormalities in MDS involve the loss of chromosomal material resulting from the loss of an entire chromosome or a part of it, due to deletions or unbalanced translocations. Among partial chromosome losses, del (5q) was found to be the most common followed by del (20q). MDS can also be associated with multiple morphologic RBC abnormalities including macrocytes, ovalocytes, dacrocytes, fragmented cells and basophilic stippling. Limited cases of MDS with elliptocytosis have been reported in the literature. Elliptocytosis encompasses a heterogeneous group of erythrocyte disorders. Although acquired cases of elliptocytosis have been reported, these are most often hereditary disorders with a variable clinical presentation from asymptomatic carriers to patients with severe hemolytic anemia. This disorder is quite rare in the Unites States (US). Mutations in protein 4.1, alpha spectrin, beta spectrin, glycophorin C and band 3 have been reported in hereditary elliptocytosis. Only 7 well reported cases of marked elliptocytosis associated with MDS have been reported in the literature. Of those 7 cases, 4 of them were associated to del(20q). All of them were elderly males and all of them had ≤ 5% bone marrow blasts. Anemia is usually moderate (median 9.4 g/dL; range 8.1–12) and thrombocytopenia is mild to moderate (median platelet count 116 x 109/L; range 46–149 x 109/L). All cases were described either in Europe (n= 1;

Rummens et al. Acta Haematologica 1986; 75:174–177
) or in Asia (n= 3;
Ideguchi et al. Br J Haematol. 1993, 75:387–92
;
Ishida et al. Cancer Genetics and Cytogenetics 1997, 108:162–165
;
Hur et al. Clin Lab Haematology, 2004, 26: 69–72
). Of these 7 cases, 3 of them were associated with protein 4.1 deficiency. To the best of our knowledge these are the first 2 cases of patients with marked elliptocytosis and MDS with del 20q abnormality reported in the US:

Patient 1Patient 2
Age/sex 82/male 79/male 
FAB classification RA RA 
Year of diagnosis of MDS 1998 1999 
WBC 3.0 x 109/L 11.5 x 109/L 
Platelets 82 x 109/L 79 x 109/L 
Hemoglobin 11.8 g/dL 10.7 g/dL 
Hematocrit 34.4% 31.9% 
Reticulocyte 4.3% NA 
LDH 350 u/L NA 
Direct Coombs Negative NA 
BM Cytogenetics 46 XY, del (20)(q11.2) 46 XY, del (20)(q11.2) 
Prior Therapy supportive care only Erythropoeitin 
Patient 1Patient 2
Age/sex 82/male 79/male 
FAB classification RA RA 
Year of diagnosis of MDS 1998 1999 
WBC 3.0 x 109/L 11.5 x 109/L 
Platelets 82 x 109/L 79 x 109/L 
Hemoglobin 11.8 g/dL 10.7 g/dL 
Hematocrit 34.4% 31.9% 
Reticulocyte 4.3% NA 
LDH 350 u/L NA 
Direct Coombs Negative NA 
BM Cytogenetics 46 XY, del (20)(q11.2) 46 XY, del (20)(q11.2) 
Prior Therapy supportive care only Erythropoeitin 
View Large

Evaluation for protein 4.1 deficiency in one of these 2 patients is currently pending.

The elliptocytosis noted in these MDS patients were most likely derived from acquired clones with abnormal development of the erythroid lineage and were associated with deletion of chromosome 20q. Patients with acquired elliptocytosis and associated MDS with del 20q chromosomal abnormality seem to have an indolent course with prolonged history of mild to moderate blood cytopenias and low risk to transformation to acute leukemia. Further research is needed to deduce the clinical significance of this subtype of MDS with this unusual RBC morphology

Topics:
chromosomes, hereditary elliptocytosis, myelodysplastic syndrome, alpha-spectrin, anemia, beta-spectrin, cancer genetics, chromosomal disorder, congenital abnormality, cytopenia

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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