Newly acquired genomic abnormalities can arise during the natural history of chronic lymphocytic leukemia (CLL). Reported frequencies range from 17 to 42%, based on several series with small numbers of patients (n ¼ 31-64) and with a limited follow-up (60-83 months) [1][2][3][4]. It has been shown that this complication appears more frequently in patients with unmutated IGVH (immunoglobulin heavy chain variable region) and after treatment. Deletion (del) of 17p13 is unusual as clonal evolution (CE) in untreated patients, and the same thing applies in patients with mutated IGVH. In the present article we report the data obtained in our series, and show that del(17p13) can occur in untreated patients, as well as in those with mutated IGVH.We retrospectively collected data from two Spanish centers. Overall, 81 patients had at least two fluorescence in situ hybridization (FISH) analyses done. The reason for repeated FISH analysis was clinical progression, although in both centers FISH was not performed on a routine basis. The probes used were: LSI p53/LSI ATM and LSI D13S319/ LSI 13q34/CEP 12 multi-color probe sets (Vysis, UK). Standard cut-off level for a deletion was determined as 10% for the probes LSI D13S319, LSI ATM, and LSI p53, and 5% for trisomy 12. A second independent observer analyzed FISH borderline results. Median time of observation after first FISH analysis was 67 months (range 16-111).The baseline characteristics of patients can be seen in Table I. Seventeen out of 81 (21%) patients had CE. In the first FISH analysis, eight out of these 17 (47%) patients had alterations: seven of them (41%) had one alteration [five cases with del(13q14), two cases with trisomy 12] and one case (6%) had two anomalies (13q 7 6 1/11q7). Median observation time between first FISH and the subsequent study with CE was 30 months (range 8-99).Regarding CE itself, 53% of the patients acquired 17p7, while 35% of the cases acquired 11q7, either an anomaly alone or in combination.The details of all the CE cases can be found in Table II, including the treatment between FISH analyses; IGVH data are added, where available.Ten cases with CE had available IGVH data, and four of these were mutated. A germline homology of 98% was used as the cut-off between VH mutated Table I. Clinical characteristics and prior therapy. With CE Without CE n 17 64 Median age (years) (range) 70 (41-80) 68 (45-86) Female (%) 8 (47) 32 (50) Rai III/IV or Binet C (%) 2/14 (14) 13/57 (23) Binet B þ C (%) 4/14 (50) 27/57 (47) Unmutated VH 6/10 NA Number of prior lines (range) 1 (0-6) 1 (0-7) CD38 þ (%) 5/11 (45) 22/53 (41) ZAP70 þ (%) 3/8 (37) 17/45 (38) Follow-up from diagnosis (months) (range) 80 (15-217) 35 (8-183) CE, clonal evolution; NA, not available.
Williams or Williams-Beuren syndrome (WBS) is a developmental disorder with multisystemic manifestations characterized by distinctive facial features, mental disability with unique cognitive and personality profiles, vascular stenoses, growth retardation, and occasional infantile hypercalcemia, caused by haploinsufficiency for genes deleted in chromosome band 7q11.23. However, with the exception of arterial stenoses caused by haploinsufficiency for the elastin gene (ELN), no specific implication of any other gene in the phenotype has been established. We present two patients with portal hypertension leading to splenomegaly and pancytopenia carrying the common 1.5 Mb WBS deletion. We propose this is an additional severe vascular complication of ELN deficiency and discuss the specific characteristics of the portal venous tract that could explain the impact of ELN deficiency in that venous territory. This complication is potentially lethal and should thus be considered in any patient with WBS and splenomegaly.
Key Clinical MessageDiamond-Blackfan anemia (DBA) is a congenital erythroid aplasia usually diagnosed in the early infancy and associated with mutations or large deletions in 11 ribosomal protein (RP) genes. Adult patients with severe, transfusion dependence, aregenerative anemia might have a genetic-in-origin disease with an atypical presentation. Late onset nonclassical DBA should be ruled out and mutations of RP genes studied.
Flow cytometry is a widely used method to study most of the hematologic malignancies. The utility of bone marrow immunophenotyping for the evaluation of patients with myelodisplastic syndrome (MDS) is currently being evaluated but most of these studies are based on the analysis of a large number of monoclonal antibodies.
OBJECTIVE: To explore the potential contribution of flow cytometry to the diagnosis of MDS using a reduced panel of conjugated monoclonal antibodies (MoAb).
PATIENTS AND METHODS: 45 bone marrow specimens from patients with a diagnosis of MDS based on morphologic and cytogenetic parameters (17 RA, 12 RARS, 5 MMCL, 9 RAEB, 2 RAEB-t), were analyzed by flow cytometry. In addition, 25 samples of bone marrow obtained from patients with cytopenias, but no diagnosis of MDS, were also studied. The panel of MoAb used was designed to identify abnormalities in the differentiation pathways of erithroid (CD71 FITC/Gly A PE/CD45 PC5) and myeloid lineage (CD 16 FITC/CD11b PE/CD13 PC5) as well as the presence of specific aberrant features in the CD34+ myeloid cell population (TdT FITC/CD7 PE/CD34 PC5). All samples were analized by two independet observers. To establish the diagnosis of MDS by flow cytometry, it was necessary to describe either immunophenotypic abnormalities in both myeloid and erithroid lineages or abnormalities in only one lineage plus description of more than 5% of CD34+ cells or abnormalities in one lineage plus description of aberrant features in the CD34+ population, regardless of its percentage.
RESULTS: In 43 of the 45 samples analyzed, flow cytometric criteria of MDS were described. Only two cases (1 RARS with normal karyotype and 1 RA with complex cytogenetics) were considered normal according to the immunophenotypic criteria (95% sensivity). Regarding the cohort control, 4 samples had flow cytometric criteria of MDS; 11 samples showed isolated antigenic aberrancies in the erithroid differentiation and the 11 samples left were considered as normal.
CONCLUSIONS: Flow cytometry may be a useful tool in the diagnosis of MDS, even analysing only two hemopoietic cell lineages. The reduced panel of MoAb described here can be widely used, is easy to be applied and shows a high sensitivity and a low cost. However, the finding of isolated immunophenotypic abnormalities in some patients without cytologic data of MDS seems to negatively influence the specificity of the technique. Nevertheless, those cases presenting an abnormal immunophenotype and normal morphology should be carefully monitored during their ulterior follow-up.
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