Search

Background. One of the principal ways to enhance the food products quality and improve the nutritional structure of the population is the introduction of non-traditional types of plant raw materials containing a balanced complex of proteins, lipids, minerals, vitamins, macro- and microelements into the diet. Methods. As an object of research, we used amaranth grain of the “Voronezhsky” variety. The processing of amaranth grain into various products was carried out on MLP-4 laboratory grinding mills with fluted and smooth microrough rollers. Results. As a result of mechanical amaranth grain processing using stock-produced technological equipment, the following amaranth processing products were derived as a raw material for the production of various bakery, confectionery and food-concentrate products: whole grain amaranth flour, low-fat amaranth flour, starchy amaranth flour, protein amaranth flour, amaranth flakes and amaranth bran. Technological scheme for producing whole grain amaranth flour consisting of third break systems has been developed. Conclusion. The yield of whole-ground amaranth flour was 97.2%, the yield of amaranth bran was 2.8%. Technological scheme for processing amaranth meal and consisting of one milling and three vibrating systems has been developed. The yield of whole-ground amaranth flour was 92%, the yield of amaranth bran was 8%. The optimum parameters of the amaranth grain hydrothermal treatment by cold conditioning were determined - in the production of amaranth flakes, the original amaranth grain are to have a moisture content of 12-13% and be binned for 2 hours. Established optimum roller space at which the yield of amaranth flakes reaches 88.9% per one pass through the roller mill is 0.1 mm.

Aim. To carry out a comparative analysis of self-rated health, medical activity, and satisfaction with the quality of medical care in public health institutions by residents of rural settlements of the Untsukul district, Republic of Dagestan. Methods. The study was conducted by the method of questioning 2643 respondents, among them 1453 women and 1181 men. Results. According to the results of the survey, the majority of the interviewed residents of Untsukul district (68.2%) are satisfied with their health. Medical activity of the population at the time of the study was 60.6%. As to respondents who applied to the medical institutions of the Untsukul district during this period, 13.5% are not satisfied with the quality of medical care in public health institutions, 23.5% are fully satisfied, 30% are not fully satisfied. Conclusion. A social survey in the form of a questionnaire is one of the most effective methods of obtaining information about the self-rated health of the population. Timely analysis of medical activity of the population, its satisfaction with the quality of medical care will improve the efficiency of the health system.

Oligonucleotide array-based comparative genomic hybridization (oaCGH) was used to investigate 60 cases of hematologic malignancies, mainly acute myeloid leukemias and myelodysplastic syndromes, in order to evaluate its sensitivity and specificity and to search for genomic alterations undetected by previous investigation with conventional cytogenetics (CC) and fluorescent in situ hybridization (FISH). On the basis of CC and FISH results, we subdivided the series into group A (36 cases with a normal karyotype after CC and/or FISH testing) and group B (24 cases with anomalies detected by CC and/or FISH). oaCGH did not show alterations in 21 cases of the group A (58.3%); in the remaining 15 cases (41.7%), it detected 19 new abnormalities (14 amplifications and 5 deletions). In the group B, oaCGH confirmed 32/55 aneuploidies detected by FISH (58.1%). The sensitivity increased at 27/33 confirmed aneuploidies (81.8%) by placing as a cutoff a mosaic of 50%. Moreover, in the cases of this group oaCGH revealed 36 new alterations (15 amplifications and 21 deletions). From these results it is possible to assess a strong overlap between results obtained by FISH and oaCGH. However, oaCGH is a reliable alternative where CC and FISH are not feasible and is able to identify new alterations unexplored by FISH.

Purpose: Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in chronic myeloid leukemia (CML) across different treatment modalities. In the imatinib era, the prognostic impact of der(9) deletions has been evaluated mainly in patients with late chronic-phase (CP) CML, giving partially conflicting results. Few data are available in the early CP setting. For this reason, in 2006, the European LeukemiaNet recommendations still considered der(9) deletions as a candidate adverse prognostic factor and required a careful monitoring of the patient., Patients and Methods: To investigate the prognostic value of der(9) deletions in early CP CML, we performed an analysis of three prospective imatinib trials of the Italian Group for Hematological Malignancies of the Adult (GIMEMA) CML Working Party., Results: A fluorescent in situ hybridization (FISH) analysis of bone marrow cells was performed at diagnosis; der(9) deletions were detected in 60 (12%) of 521 evaluable patients. At 60 months, the cumulative incidence of complete cytogenetic response and major molecular response-and the probability of event-free survival, failure-free survival, progression-free survival, and overall survival-in patients with and without deletions were not statistically different., Conclusion: Our data strongly support the notion that, when investigated by FISH, der(9) deletions are not a poor prognostic factor in patients with early CP CML treated with imatinib.

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin's Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as 'low expressing' (< 20% of tumor cells) or 'highly expressing' (>or= 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p=0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p=0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (approximately 20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells ( approximately 70% at 5 year). This correlation was statistically significant (log-rank test, p=0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.

In chronic myeloid leukemia, different methods are available to monitor the response to therapy: chromosome banding analysis (CBA), interphase fluorescence in situ hybridization (I-FISH), and real-time quantitative polymerase chain reaction (RT-Q-PCR). The GIMEMA CML WP (Gruppo Italiano Malattie Ematologiche Adulto Chronic Myeloid Leukemia Working Party) has performed a prospective study to compare CBA and I-FISH for the definition of complete cytogenetic response (CCgR). Samples (n = 664) were evaluated simultaneously by CBA and I-FISH. Of 537 cases in CCgR, the number of positive nuclei by I-FISH was less than 1% in 444 cases (82.7%). Of 451 cases with less than 1% positive nuclei by I-FISH, 444 (98.4%) were classified as CCgR by CBA. The major molecular response rate was significantly greater in cases with I-FISH less than 1% than in those with I-FISH 1% to 5% (66.8% vs 51.6%, P < .001) and in cases with CCgR and I-FISH less than 1% than in cases with CCgR and I-FISH 1% to 5% (66.1% vs 49.4%, P = .004). I-FISH is more sensitive than CBA and can be used to monitor CCgR. With appropriate probes, the cutoff value of I-FISH may be established at 1%. These trials are registered at http://www.clinicaltrials.gov as NCT00514488 and NCT00510926.

Background: Plex-B1, the receptor of Sema4D, has been implicated in tumour growth, angiogenesis and metastasis. The binding of Sema4D to Plex-B1 can trigger the activation of Met tyrosine kinase, thereby promoting cell dissociation and invasive growth. We tested the hypothesis that the expression of Plex-B1, either alone or in association with Met, can be of predictive value for tumour progression., Methods: The expression and distribution of Plex-B1 and Met were investigated by immunohistochemistry and immunofluorescence in 50 human neoplasias originating in the breast and ovary, and correlated with clinical-pathological data at diagnosis., Results: Plex-B1 and Met were individually expressed in 14% and in 24% of the tumours, respectively. Plex-B1 and Met were co-expressed in 24/50 cases (48%), and in the majority of these (83%) Met was tyrosine phosphorylated. The expression of Plex-B1 or Met alone showed no significant correlation with tumour aggressiveness, whereas advanced stage tumours (III-IV) frequently showed Plex-B1-Met double-positive (9/13). Tumours co-expressing Plex-B1 and Met were characterised by worse grading and higher incidence of lymph node metastases. Out of 22 tumours with lymph node metastases, as many as 19 were Plex-B1 and Met double-positive (p=0.0008), and 17 expressed phosphorylated Met (p=0.002)., Conclusion: Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met.

Malignant schwannoma is an uncommon but aggressive sarcoma that most commonly arises in young and middle-aged adults. We present a 28-year-old male patient with a recurrent chest wall malignant schwannoma. An FDG PET/CT was performed to evaluate the management of the patient. The PET/CT images showed hypermetabolic mass lesions in the left upper chest wall and increased FDG uptake in the left axillary region. The pathologic results confirmed the PET findings. We conclude that FDG PET/CT could play an important role in the staging, restaging, and post-therapy follow-up of malignant schwannomas.

The present study investigated whether the expression of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (cFLIP) conveys prognostic information in non-Hodgkin lymphomas (NHLs). cFLIP expression was quantified by immunohistochemistry and immunofluorescence in biopsy specimens from 86 NHL patients for whom clinical information was available. NHL malignancy was graded as high/intermediate or low according to the World Health Organization Classification of Lymphoid Neoplasms. cFLIP was positive in 23 of 45 high-/intermediate-grade NHLs and in 25 of 41 low-grade NHLs. Negative expression of cFLIP was associated with the presence of apoptotic cells in the tumour mass, regardless of the histotype and of the malignancy grade. In NHLs positive for cFLIP, 11 of 23 (48%) high-/intermediate-grade cases and 18 of 25 (72%) low-grade cases showed a bad outcome. In NHLs negative for cFLIP, only four of 22 (18%) high-/intermediate-grade patients and 12 of 16 (75%) low-grade patients achieved complete remission. All these correlations were statistically significant. The correlation of cFLIP expression with clinical outcome was independent of therapy, whether or not it included anti-CD20 antibody (Rituximab). The present findings strongly indicate that cFLIP is a reliable predictor of tumour progression and clinical prognosis in NHLs of low grade of malignancy.

A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust, however no conclusive data have been reported up to now about morphological precursors of these tumors, mechanisms of carcinogenesis and role of p53 gene. Immunohistochemical overexpression of protein p53 (DO7 clone) by epithelial cells of ethmoidal mucosa was investigated on 60 woodworkers occupationally exposed for a minimum of 10 years, on 50 functional and/or esthetic nasal surgery patients (control group) and on 15 cases of intestinal-type adenocarcinoma, 10 of these involving subjects who had a longtime exposure to wood dust. In almost all the woodworkers (92%) the normal ciliated epithelium showed tracts of squamous metaplasia. The mean percentage of p53-positive cells in woodworkers and in controls was 28.6 and 7.97%, respectively, in metaplastic epithelium (P<0.001), 11.7 and 2.08% in ciliated epithelium (P<0.001), 12.46 and 1.03% (P<0.001) in the sero-mucous glands of the nasal stroma. Both in tracts of metaplastic epithelium and in those of ciliated epithelium, positive cells were distributed in basal and suprabasal layers. A high number of p53-positive cells was also observed in the normal ciliated epithelium close to the neoplastic cells, of intestinal-type adenocarcinomas affecting subjects with longtime exposure to wood dust. Moreover, a higher number of p53 positive neoplastic cells was showed by the cases occurring in occupationally exposed patients than by the others. The following conclusions can be drawn: (1) in the ethmoidal mucosa, a region at high risk of carcinogenesis in subjects exposed to wood dust, epithelial cells overexpress p53 protein, and this may be linked to the presence of p53 gene mutations; malignant transformation, as at other head and neck sites, may thus occur through this pathway; (2) the presence of p53 overexpression in sero-mucous glands is in keeping with the histogenesis of some tumors from these structures; (3) since tumors of nose and paranasal sinuses, mainly adenocarcinoma, are recognized as occupational neoplasias, immunohistochemical evaluation of p53, perhaps combined with molecular methods, could be the first step to detect subjects at high risk of carcinogenesis among woodworkers.

In a previous epidemiological study on acute myelocytic leukemia (M. M. Crane et al., Cancer Epidemiol. Biomark. Prev., 5: 639-644, 1996), clonal aberrations in chromosome 8 have been reported to be in excess in smokers and in workers exposed to paints. In that study, cytogenetics was performed after therapy. In our report, we describe a population-based survey on nonlymphocytic leukemias in northern Italy, in which 79 patients (acute myelocytic leukemia, myelodysplastic syndromes, or other nonlymphocytic leukemias) were studied before cytotoxic therapy. We found 9 aberrations involving chromosome 8 (six +8, two -8, and one translocation), whereas abnormalities involving chromosomes 5 and 7 occurred with a low frequency compared with previous studies. Aberrations involving chromosome 8 were associated with smoking (odds ratio, 6.3; 95% confidence interval, 0.9-42.3; among smokers of 10 or more cigarettes/day: odds ratio, 14.2; 95% confidence interval, 1.4-142.3); +8 aberrations were found in 1 of 24 nonsmokers and in 5 of 38 smokers. Three +8 aberrations were found in 22 subjects potentially exposed to solvents or polycyclic aromatic hydrocarbons. The low frequency of chromosome 5 and 7 aberrations in our population-based series (compared with other studies) can be attributed to the recruitment before cytotoxic therapies. Aberrations involving chromosome 8 (particularly +8) were associated with smoking habits. Chromosome 8 includes the c-myc oncogene.

Several lines of evidence have pointed to the involvement of a viral agent in the pathogenesis of Hodgkin's disease (HD). Therefore we investigated the presence of human herpesvirus type 7 (HHV-7) in 53 cases of HD by polymerase chain reaction (PCR), DNA in situ hybridization (ISH) and immunohistochemistry. HHV-7 DNA was frequently detected (68% of the cases) in HD biopsies by PCR independently of the histological type, whereas only 32% (P<0.05) of positive cases were found in 19 reactive lymph nodes. However, by applying the quantitative PCR technique, the majority of the samples showed a low level of viral load. Moreover, ISH for HHV-7 DNA was positive in a low number of small T lymphocytes and consistently negative in Hodgkin and Reed-Sternberg (HRS) cells, which appeared negative for HHV-7 also at immunohistochemistry. These results indicate that the high frequency of HHV-7 infection in HD: (i) is probably non-productive, (ii) mainly involves small lymphocytes belonging to the T-lineage, and (iii) is probably due to the recruitment of non-malignant reactive cells in HD tissue.

Background and Objective: In their review of the Rye histopathological classification of Hodgkin's disease, Bennett and coworkers have proposed that the nodular sclerosis (NS) type should be divided into two diagnostic categories on the basis of their clinical behaviour. In order to evaluate whether the proliferative activity of HD cells might correlate with histology in NS subtypes, we reviewed and re-evaluated cryostat and paraffin-embedded sections from 80 cases sent to our centre from 1986 to 1991., Methods: In the present study, we investigated the growth cell fraction of 53 cases of Hodgkin's disease with nodular sclerosis by using Ki67 and MIB1 monoclonal antibodies to determine whether proliferative activity is associated with different pathological subtypes and prognostic categories. Eight cases with an interfollicular pattern and 19 with mixed cellularity were also investigated. The results in each group were compared to the others., Results: The values of Ki67 and MIB1 were highly correlated (r = 0.88). In Hodgkin's disease with nodular sclerosis, two groups with significantly different growth fractions were morphologically identified: one with lymphocyte predominance and mixed cellularity subtypes, another composed of cases with variously extensive lymphocyte depletion. The figures were compared with those of interfollicular subtype, which fell into the first group, and of mixed cellularity type, in which the proliferative cell activity was significantly higher than in the second nodular sclerosis group. In all cases, Reed-Sternberg and Hodgkin cells accounted for the majority of the cell growth fraction, although a variable percentage of T-lymphocytes were also Ki67- or MIB1-positive. Taking the median value (15%) of MIB1 positive cells as a cut-off, a significant correlation (p = 0.05) was observed between MIB1 positivity and bulky disease, and a good trend (but not a significant relationship) between MIB1 and overall survival, disease-free survival, staging and the clinical response to therapy., Interpretation and Conclusions: Assessment of the growth cell fraction in Hodgkin's disease with different nodular sclerosis patterns provides biological support for the morphological reclassification of their degree of malignancy into two main groups with different impacts on the clinical parameters and a possible relation with the outcome of treatment.

Human herpesvirus-6 (HHV-6), a T-lymphotropic double-stranded DNA virus highly endemic in human populations, has been suggested to play a possible role in the development of lymphoid neoplasms, especially Hodgkin's disease. To investigate this point, we evaluated the presence and distribution of HHV-6 DNA by Southern blot, nested polymerase chain reaction, and in situ hybridization in a series of lymphoproliferative disorders including 73 Hodgkin's disease cases, 15 non-Hodgkin lymphomas, and 19 reactive lymph nodes. A high prevalence of HHV-6 infection was observed within the Hodgkin's disease category by polymerase chain reaction (38 of 52, 73%) and in situ hybridization (47 of 57, 82.4%); however, a similar prevalence was found in non-Hodgkin's lymphomas (10 of 15, 66.6%) and reactive lymph nodes (13 of 19, 68.4%). In no case did Southern blot detect viral DNA, suggesting that the neoplastic tissue contained a low number of HHV-6 copies. In situ hybridization showed that the HHV-6 positivity was restricted to lymphocytes, whereas Hodgkin and Reed-Sternberg cells were consistently negative. Immunohistochemical staining with specific monoclonal antibodies against viral structural proteins was also negative, indicating the absence of a productive infection. No relationship was observed between HHV-6 positivity and histological type, clinical parameters, and outcome of the disease. In the same series, a high proportion of cases (39 of 52, 75%) showed the presence of the Epstein-Barr virus (EBV) genome by polymerase chain reaction; In situ hybridization for Epstein-Barr-virus-encoded small RNA and immunohistochemical detection of latent membrane protein-1 gave similar results (73.6% of positive cases with both methods). In 54.9% of the cases, both sequences of HHV-6 and Epstein-Barr virus DNA were found, suggesting that a synergism of the two viruses may occur. However, the lack of detectable HHV-6 DNA in Reed-Sternberg and Hodgkin's cells seems to argue against such an interpretation. Based on these results, HHV-6 does not appear to play a specific role in the pathogenesis of Hodgkin's disease.

The cell proliferative activity of the clinico-pathologically heterogeneous non-Hodgkin's lymphomas (NHL) included in the intermediate grade F category of the Working Formulation (WF) was investigated. S-phase fraction with flow cytometry on cell suspensions, and Ki67 on frozen tissue sections were performed in 42 F NHL. An avidin-biotin immunocomplex method was used and 1000 cells from 10 representative fields were counted. DNA content, S-phase and Ki67 were also detected in 194 NHL covering the whole spectrum of the WF. DNA content anomalies were found in 52 of 194 NHL. Their incidence, like that of S-phase fraction and Ki67 positive cells, progressively increased from low- to high-grade. A linear correlation was found between Ki67 and S-phase (r = .59). Using the median value of proliferating cells obtained with both procedures as a cut off, two very different groups of lymphomas could be distinguished within a series of 42 F-intermediate NHL: with low and high proliferative cell activity (p < .0001) that were termed F(low) and F(high), respectively. A intermediate group was placed between them. It differed significantly from the others if Ki67 was used but only from the F(high) group if the S-phase fraction analysis was applied. No significant differences were seen when comparing F(low) with the single categories of low-grade NHL and F(high) with H high-grade NHL; no significant differences were found between F(high) and G, and between G and H categories. The existence of distinct groups of NHL in the F category, as defined by biological parameters assessing the cell proliferative activity, indicates that this category includes biologically heterogeneous lymphoma subtypes with different grades of aggressiveness. The results also indicate that the G intermediate category displays proliferation indices similar to those of H high grade category.

B-cell clonality was demonstrated in a typical nodular paragranuloma case (NP) by both immunoglobulin (Ig) surface analysis and Ig genes rearrangement studies. On frozen sections, immunostaining for Ig light chain expression revealed a clear-cut predominance of Ig lambda-expressing cells, recognizable as both small lymphocytes and lympho-histiocytic (L&H) cells. Accordingly, molecular analysis of the Ig genes showed a monoclonal rearrangement of the lambda chain gene, although no specific pattern of heavy chain gene rearrangement could be detected by JH analysis. The C lambda rearranged band was identified with two different restriction enzymes, excluding the hypothesis of a genomic polymorphism. Furthermore, the C kappa gene was almost completely deleted, indicating that the developmental hierarchy of Ig genes rearrangement has been respected. The molecular pattern of the C lambda hybridizing band was consistent with monoallelic rearrangement of almost the entire DNA sample, indicating that clonal proliferation was not limited to L&H cells, but also involved surrounding lymphocytes. This finding is in keeping with the immunohistochemical evidence of a lambda light chain restriction on both L&H cells and small lymphocytes, pointing to a close relationship between these two cell types. Our results as a whole suggest that L&H cells and B lymphocytes share a common origin and may both be involved in clonal proliferation in NP.

An identical extra derivative chromosome resulting from a translocation between the long arm of chromosome 1 and the short arm of chromosome 9, +der(1q9p), has been observed in three patients with a myeloproliferative disorder. Two patients had polycythemia vera in transformation (erythroleukemia in one patient and refractory anemia in the second), whereas the third patient had myelofibrosis which later evolved into acute myelomonocytic leukemia. The two patients who developed overt leukemia did not receive any previous cytotoxic treatment. Non-isotopic in situ hybridization was performed in two patients, allowing for the localization of the breakpoints in 1q12 and 9q12. A similar rearrangement has been previously described in patients with polycythemia vera, either at diagnosis or in advanced stages of the disease. These data suggest that this chromosome abnormality may be consistently associated with myeloproliferative disorders showing a high propensity to transformation, which is not treatment related, and the finding of the +der(1q9p) may represent a poor prognostic sign when observed in the chronic phase.

The proliferative induction by hemopoietic growth factors may provide a useful tool to improve the mitotic yield of hemopoietic cells, allowing a more accurate cytogenetic analysis in hematologic malignancies. For such a purpose, we studied the effects of the recombinant human IL-3 (rhIL-3) on the mitotic index and the karyotype of bone marrow cells from 14 patients with myelodysplastic (MDS) and myeloproliferative syndromes (MPS). The mitotic response to IL-3 of normal bone marrow samples was also evaluated. Total bone marrow cells were cultured for 24 to 72 hours either in presence or absence of rhIL-3. In most cases, IL-3--stimulated samples showed a considerably higher (4-70 times) mitotic index than unstimulated controls. Although a great patient-to-patient variability was observed, a common pattern of mitogenic response to IL-3 emerged among MPS, MDS, and normal cases. At 48 hours of incubation, the mean mitotic index from MPS and MDS cases stimulated with IL-3 was significantly higher (p less than 0.01) than unstimulated controls, whereas the mean mitotic increase from normal samples did not reach statistical significance (p greater than 0.1). Even though not statistically evaluable, a similar trend of response was observed at 24 and 72 hours of culture. Chromosome studies of MPS and MDS cases showed the same karyotype either in stimulated and unstimulated samples.

In a patient with idiopathic myelofibrosis (MFI) that had progressed to acute nonlymphoid leukemia (ANLL) after a long-lasting cytotoxic treatment, we observed two karyotypically independent cell populations, one showing trisomy of chromosome 8 as the only anomaly and one with an unbalanced translocation t(5;17)(q11) resulting in partial monosomy of 5q and 17p. The overall karyotypic configuration suggested that chromosome changes occurred as secondary events during the multistep process of leukemogenesis. The probable sequence of cytogenetic events in this patient and a review of the literature indicated that the t(5;17) may represent a therapy-induced abnormality nonrandomly related to the terminal phase of myeloid disorders.

The prognostic value of the FAB classification, bone marrow histology, Bournemouth score, and chromosome findings was studied in 88 patients with primary myelodysplastic syndromes. The median survival for the whole group of patients was 22 months (RA 61.7 months, RARS 31.6 months, CMML 15.7 months, RAEB 10.3 months, and RAEBt 8.2 months). Chromosomal abnormalities were found in 37 of the 70 patients investigated (52%). Only the differences in survival between patients with complex versus normal karyotype were statistically significant (p = 0.02). The presence of small blastic cells, located away from the endosteal surface (abnormal localization of immature blasts or ALIP) appears to be a major prognostic factor in predicting the duration of survival and progression to ANLL, especially in the FAB subgroups RA and RARS. Median survival for the 22 ALIP- cases with RA/RARS was 65 months, compared with 31 months for the ALIP+ cases (p = 0.0006). Nine ALIP+ patients (53%) developed ANLL in contrast to 3 (13%) of the ALIP- cases (p = 0.008). By redefining ALIP and evaluating the number and characteristics of the accompanying cells, histological subtypes were distinguished correlating largely with the FAB subgroups. Our findings demonstrate the prognostic importance of bone marrow biopsy and quantifying the complexity of bone marrow chromosome changes. It should be helpful in evaluating current attempts to find effective treatment for patients with MDS.

Three cases of t(11;21)(q24;q11.2) myelodysplastic syndromes (MDS) showed karyotypic evolution resulting in the presence of two der(11)t(11;21) without normal chromosome 11 and with partial trisomy 21q. In one of these, we performed further molecular cytogenetic investigations which showed 1) that this rearrangement led to changes in the dosage and location of both c-ets 1 and c-ets 2 protooncogenes; and 2) that the presence of two 11q + chromosomes did not result from a nondisjunction, but that a second chromosome rearrangement had occurred. The final genetic imbalance resulting from this cytogenetic change involves at least hemizygosity for some sequences on the long arm of chromosome 11, including c-ets 1, plus trisomy for the most part of the long arm of chromosome 21, including c-ets 2.