Marcela Sarmiento

Structural aberrations of chromosomes 17 and 12 in chronic B-cell disorders.

Abstract: Objectives: Genomic aberrations can now be identified in approximately 80% of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. In the present study, four new structural changes involving chromosomes 17 and 12 in CLL/SLL patients are described.

dup(12)(q13–q22) and 13q14 Deletion in a Case of B-Cell Chronic Lymphocytic Leukemia

Cases with partial trisomy 12 have rarely been found in B-cell chronic lymphocytic leukemia (CLL). We report our clinical, cytogenetic and fluorescence in situ hybridization (FISH) findings in a CLL patient with a duplication of part of the long arm of chromosome 12 between bands q13–q22. This patient was the only case with this duplication among the 112 cases (0.9%) of CLL cytogenetically analyzed in our laboratory. FISH studies using unique-sequence specific probes for the RB-1 (retinoblastoma) gene and the D13S319 locus at the 13q14 band showed a monoallelic loss for the D13S319 locus (20% of cells) with a diploid RB-1 gene. Our case showed an atypical morphology (35% prolymphocytes), a high proliferation rate and progression of the disease, indicating that the duplication of this region may be equivalent to complete trisomy 12 in CLL patients.

CD8 Expression in a Case of Chronic Lymphocytic Leukemia with Trisomy 12

We report a case of B-cell chronic lymphocytic leukemia (B-CLL) with aberrant expression of the T-cell-associated antigen CD8, as revealed by two-color flow-cytometric analysis. DNA studies showed immunoglobulin heavy-chain gene rearrangement, but not of γ-chain T-cell receptor, confirming the B-cell origin of the neoplastic cells. Ploidy analysis showed a tetraploid population and high S-phase fraction. B-CLL cells also carried trisomy 12, detected by fluorescence in situ hybridization. The identification of more cases with the same features would be necessary to establish the prognosis of this subtype of B-CLL.

Anti-Epo and anti-Tpo antibodies in myelodysplastic syndromes

To the Editor: We have read a previous report by Voulgari et al. (1) concerning the lack of anti-erythropoietin (Epo) antibodies (abs) in myelodysplastic patients. Myelodysplastia (MDS) arises from genetic defects. Epigenetic phenomena contribute to cytopenia and proliferation, revealing heterogeneous phenotypes (2). Based on the occurrence of autoantibody and clonally expanded T cells in MDS (3, 4), we were prompted to evaluate anti-Epo and anti-Tpo antibodies in these patients. Literature reports on this subject are quite scarce. Forty-five patients and 15 healthy donors were enrolled prospectively. Endogenous Epo and Tpo were measured by the ELISA method (Quantikine, R&D Systems). Our Epo and Tpo normal ranges were 3.3– 16.6 mIU mL and 15–190 pg mL, respectively. Briefly, to assess anti-Epo and anti-Tpo abs, 250 lL (micro liter) of highly purified rHU-Epo and Tpo, iodinated with I as previously described (5, 6), were incubated overnight at 4 C with 20 lL (micro liter) of patients’ or controls’ sera. Afterwards, radioactivity was measured by a c-counter. Using international criteria, 26/45 patients were diagnosed as having MDS (Table 1). Myelodysplastic patients showed significantly higher Epo levels than controls: MdI 37 mIU mL (1.7–4400 mIU mL) vs. 9.2 mIU mL (4–15 mIU mL) (P 1⁄4 0.03), respectively, while the Epo content of most non-myelodysplastic patients was normal: Md 12.8 mIU mL (1.6–530 mIU mL). Myelodysplastic patients and controls had similar Tpo values: Md 75 pg mL (14.9–2100 pg mL) and 96.5 pg mL (15–190 pg mL) (P 1⁄4 0.05), respectively. Five patients showed increased values: two RA, two RAEB-t and one refractory tricytopenia. Non-myelodysplastic patients had normal Tpo levels: Md 44 pg mL (14.9–170 pg mL). Neither the patients nor the controls showed detectable abs against either Epo. or Tpo. Karyotype alterations found in four MDS patients showed no additional information. In agreement with literature reports, we observed that at similar degrees of anemia, myelodysplastic patients had higher Epo levels than non-myelodysplastic ones. Compared with Voulgari’s patients, we found lower Epo levels. However, Epo and Tpo levels might not predict the abs presence, since a lack of correlation between them has been noticed in amegakaryocytic thrombocytopenic purpura and pure red cell aplasia (7–9). Regarding Tpo, the major regulator of megakaryopoiesis, cirulating levels are controlled by specific binding to its receptor, c-mpl, expressed on megakaryocytes and platelets, leading to its internalization and degradation. Tpo levels are different depending on the disease, and may keep