Acute Leukemia After a Primary Myelodysplastic Syndrome: Immunophenotypic, Genotypic, and Clinical Characteristics

• Published in: Blood 1991-08, Vol.78 (3), p.768-774
• Main Authors: Miguel, J.F.San, Hernandez, J.M., Gonzalez-Sarmiento, R., Gonzalez, M., Sanchez, I., Orfao, A., Canizo, M.C., Borrasca, A.Lopez
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Biological and medical sciences; Biomarkers; Bone Marrow - pathology; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Genes, Immunoglobulin; Genotype; Hematologic and hematopoietic diseases; Humans; Immunoglobulin Constant Regions - genetics; Immunophenotyping; Leukemia - blood; Leukemia - genetics; Leukemia - immunology; Leukemia - pathology; Medical sciences; Middle Aged; Myelodysplastic Syndromes - complications; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - immunology; Restriction Mapping
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.3.768.768

We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-β, -γ , and -δ and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryo-cytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and pheno-typic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10 , TdT+ ). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblasts and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration, γ and δ gene rearrangements were found in 21% and 37% of these acute transformations, respectively. The TCR-0 and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripo-tent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.