No abstract

The biological and clinical importance of cytogenetic analysis in myelodysplastic syndrome (MDS) and in acute myeloid leukemia (AML) is being increasingly recognized. Recently, cytogenetic similarities were noted between elderly de novo AML and secondary AML, suggesting common etiopathogenetic mechanisms. In the present study we analyzed the cytogenetic similarities between patients with AML of different age and patients with MDS consecutively diagnosed during a 5-year period at a single, primary referral, hematologic center. Of 246 patients aged Ͻ86 years, 195 (80%) had a cytogenetic study at diagnosis. Informative metaphases were obtained in 182 cases (93%), including 17 (9.3%) with secondary MDS/AML. Patients were classified according to FAB criteria and were subdivided into four groups: (1) 'early MDS': 42 patients with MDS of FAB subtypes other than refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-T); (2) 'late MDS': 35 patients with RAEB and RAEB-T; (3) 'old AML': 48 patients with AML aged 65 to 85 years; (4) 'young AML': 57 patients with AML aged Ͻ65 years. Results showed that 'late MDS' and 'old AML' had striking cytogenetic similarities both in the frequency of normal karyotypes (31% and 27%), single abnormalities (14% and 13%), double abnormalities (17% and 14%), complex karyotypes (37% and 46%), and numerical abnormalities (89% and 93%), as well as in the frequency of rearrangements involving chromosome 5 (20% and 31%) and 7 (27% and 27%). The only difference between the two groups was found in the median number of chromosomes involved in complex karyotypes (5 vs 8; P = 0.03). 'Early MDS' had significantly less complex karyotypes (21%; P Ͻ 0.05), but its cytogenetic features resembled otherwise those of 'late MDS' and 'old AML', and any significant difference disappeared when patients with chronic myelomonocytic leukemia (CMML) were excluded. CMML markedly differed from other MDS subtypes in the frequency of normal (57%) and of complex karyotypes (6%). Secondary MDS/AML and AML with trilineage dysplasia shared the same cytogenetic features of 'late MDS' and 'old AML'. 'Young AML' strikingly differed from all other groups, particularly in the higher frequency of balanced translocations (29%; P Ͻ 0.001) and single karyotype abnormalities (32%; P Ͻ 0.02), and in the lower frequency of complex karyotypes (19%; P Ͻ 0.01) and of chromosome 5 (2%; P Ͻ 0.001) and 7 (9%; P Ͻ 0.01) involvement. We conclude that in a population-based series of patients, the cytogenetic profile of MDS, particularly of RAEB/RAEB-T, was nearly identical to that of elderly patients with AML both in the frequency and in the type of chromosomal abnormalities. These results support the possibility that MDS and AML of elderly patients may represent the same disease seen at different stages of evolution. Leukemia (2000) 14, 636-641.

Plasminogen (PC), urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) are the main molecules involved in fibrinolysis and in many other physiological and pathological processes. In the present study we report that human t-PA, purified from human melanoma cells, and PG, purified from human plasma, both contain P-Tyr residues, as revealed by immunoblotting analyses with monoclonal anti-P-Tyr antibodies. In addition HPLC amino acid analysis of acid-hydrolyzed t-PA, PG and u-PA, shows that: (i) P-Ser and P-Tyr residues are present in t-PA; (ii) P-Thr and P-Tyr are present in PG; (iii) P-Ser, P-Thr and P-Tyr are present in u-PA. The utilization of monoclonal anti-P-Ser and anti-P-Thr antibodies in immunoblotting experiments has confirmed these data which indicate that phosphorylation is a common feature of PAS and of PG.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. Methods: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. Results: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. Conclusions: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes. K E Y W O R D SChromosomal microarray analysis (CMA), clinical marker identification, detection rate, pathogenic

The relationship between chromosomal abnormalities and the month of conception could turn out to be useful in estimating the actual risk in pregnancy, if confirmed by other studies. The observed June lowest rate might indicate an association between chromosomal abnormalities and the maximum number of daylight hours throughout the year (summer solstice). We cannot explain the unusual findings concerning Robertsonian translocations that were only found for conceptions in December. This may be related to the annual minimum daylight hours (winter solstice) as opposed to the summer solstice.