deI 11 ( q 23 ) as a prognostic factor ofiron overload in refractory anemia with ringed sideroblasts

Myelodysplastic syndrome (MDS) is acIonaI pluripotent stem cell proliferation. The term gathers together a group of disorders that show hematological cell displasia with different leveIs óf peripheral cytopenia, gene~ally with hypercellular bone marrow. Defective maturation is associated with the precursor cell proliferation. Usually, patients are older than 50 years, MDS being rare in childhood and adolescence, and symptoms relate directly to cytopenia. The etiology is almost alwaysunkn9wn (primary MDS) but can be secondary to myelotoxic drugs like the antineoplastic ones (secondary MDS).

FAB classification has established 5 subtypes I: refractory anemia(RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess of blasts(RAEB), refractory anemia ~ith excess of blasts in transformation (RAEBt) and chronic myelomonocytic leukemia (CMML), though some clinicaI presentations do not fit into any of them, like MD~with marrow fibrosis or hypocellularity.
Around 80% of the patients present karyotype abnormalities in marrow cells, the most frequent being: trissomy 8, loss of part of the long .arms of chromosomes 5,7,9,20  or 21, and monossomy 7.or 9. 2 These abnormalities are of independent prognostic value.Vorhoef et al.(1991) studied karyotype prognostic importance in MDS patients and observed differ~nt survival times among patients with complex karyotype (7 months of survival) versus single abnormalities (21 months) versus normal karyotype (30 months).
Evolution follows the subtype.So, benign subtypes like RA and RARS rarely evolve into acute leukemia, and the patient r~mains with chronic anemia refractory to therapy.The subtypes RAEB, RAEBt and CMML are more aggressive in that 30 to 50% of the patients evolve into acute leukemia with mean survival of 5 to 10 months for the first two, and 20 months for CMML.Acquired RARS is a chronic macrocytic anemia related to a disorder in heme biosynthesis, ineffective erythropoiesis without reticulocytosis and mitocondrial iron overload that leads to the presentation of more than 15 ringed sideroblasts per 100 erythroblasts.Only 10% evolve into acute myeloid leukemia (AML).Serum iron, ferritin and transferin saturation leveIs are high, as well as in bone marrow, as shown by cytochemical staining.
Here, the case of a patient with RARS and chromosomal abnormality deI 11(q23) with iron overload is presented.
Bone marrow iron was abundant and there was 41 % sideroblasts, 27% of which were ringed.Bone marrow biopsy (iliac bone) had 70% cellularity with erythroid hyperplasia and granulocytic proliferation fitting the criteria for MOS diagnosis.Ham test was negati ve and neutrophil alkaline phosphatase score was 101(nl=15-75).Fetal Hb 0.6%.
The patient was followed up and presented a slight clinicaI and hematological improvement for a short period of time (Fig 1).Afterwards, she presented an episode of fever, hepatomegaly and hemolysis due to infection with hemoglobin falling to 2.5g% and an increase of indirect bilirrubin and OHL (1.7 and 1121 respectively).11q in patients previously exposed to epipodophyllotoxins have also been described. 3I 11q has been described in different MDS subtypes, though it is more frequent among RA and RARS.Musilova et aI.have found 13.8% del11q in RA and 9.9% in MDS .
It seems that around 30% of RARS patients have chromosomal abnormalities and del11q is found in 7% to 20% of these cases.Many works show different break regions in chromosome 11, from q 14 to q23.Thus, ferritin H chain gene located at 11q 14 would not always be involved in these abnormalities.Mecucci et aI.(1987)  observed that deI 11q was related to bone marrow iron overload and to an increase in ringed sideroblasts, among 13 patients with MDS retrospectively studied.
Considering that the patient received 90 red blood cell transfusion packs and that each one contained from 1515 200 to 250mg of iron, resulting in an iron accumulation equal to 22,500mg , such a high ferritin leveI is not justified.Now, if each 1ug/L of serum ferritin is equivalent to 8mg of stored iron, the 6,500mg/L found would mean 52,000mg of iron, ie effectively more than twice the amount administered by transfusions:However, this could be justified by the chromossomal abnormality that predisposes to iron overload.It should also be recalled that at diagnosis, the patient had bone marrow iron overload demonstrated by Perls staining. 4he present report describes a clinically typical MDS RARS case wi.th an unusual acquired karyotypic abnonnality that predisposes to non random iron overload.Future molecular studies must be done to identify its meaning since other hematological disorders have the same cytogenetic alteration.