Search

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPLannotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level <11 g/dl, to circulating blasts ⩾3%, and to CALR-unmutated genotype, 1 point to platelet count <150 × 109/l and to constitutional symptoms, and 0.15 points to any year of age. Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) allocated SMF patients into four risk categories with different survival (P<0.0001): low (median survival NR; 133 patients), intermediate-1 (9.3 years, 95% CI: 8.1-NR; 245 patients), intermediate-2 (4.4 years, 95% CI: 3.2–7.9; 126 patients), and high risk (2 years, 95% CI: 1.7–3.9; 75 patients). Finally, we found that the MYSEC-PM represents the most appropriate tool for SMF decision-making to be used in clinical and trial settings.

Summary Six cases are reported of variant Ph′ translocations found among 240 patients with Ph′-positive CML. Five cases had a three-chromosome rearrangement involving, in addition to chromosomes 9 and 22, chromosomes 7, 4, 2(two), and 3 respectively, and one case had a two-chromosome rearrangement 22/5. A review of the literature revealed that three- and two-chromosome variant Ph′ translocations are observed with equal frequency. It is postulated that all variant translocations are indeed three-chromosome rearrangements, that the specific event for the formation of the Ph′ chromosome is the reciprocal translocation 9/22, and that the transposition of regions 9q34 and 22 (q11→qter), plays a major role in the development of CML.

Two human cell lines (GL15 and GL22) derived from glioblastoma multiforme were established and characterized by immunohistochemical and cytogenetic techniques. The expression of glial fibrillary acidic proteins and the karyotype were analyzed at different passages for both cell lines. The course of marker-pattern differed in the two cell lines. The main findings were a cell-density-dependent expression of glial fibrillary acidic protein in the cell line GL15 at all passages and a decreased expression of this protein over time in the cell line GL22. Both cell lines had hyperdiploid karyotypes and exhibited glioma-specific chromosomal abnormalities (gain of chromosome 7 and loss of chromosome 10). In the GL15 cell line no relevant chromosomal changes were produced during culturing, whereas in the GL22 cell line a hypodiploid clone appeared at the 42nd passage. The immunohistochemical and cytogenetic data resulting from this study confirm that the two cell lines established in our laboratory originated from astrocytic tumor cells.

Trisomy 7, trisomy 10 and loss of the Y chromosome have been found by some authors in presumptive normal parts of human kidneys. We describe cytogenetic findings in short-term cultures from 58 biopsies obtained from non-neoplastic and neoplastic (renal cell carcinoma, RCC) tissues from the same kidney, the same types of tissues from independent kidneys, and tissue from kidneys without neoplasia. The results indicate the following. Non-neoplastic tissue from kidneys involved in RCC have (in mosaics) trisomies 5, 7, 10, 18 and loss of the Y as non-random clonal changes. They are not the result of local metastasis but are also found in kidneys with non-tumoral chronic pathologies and should thus not be considered specific for RCC. They are neither culturing artefacts nor a general phenomenon found in cultured normal solid tissues, but are acquired abnormalities, possibily related to various reactive cellular states in the tissues that are histologically normal.

Cytogenetic analysis of primary cell cultures from human atherosclerotic fibrous plaques revealed clonal chromosome abnormalities in 13 of the 18 cases studied. Loss of the Y chromosome and del(13)(q14) were present as single clonal abnormalities in eight cases; in five cases separate clones were found involving loss of the Y and a XXY karyotype, trisomy 10 and 18, loss of the Y and trisomy 7. A variety of single numerical and structural abnormalities were present in all but two of the 18 cases. Immunocytochemical studies were performed on cells from the same cultures used for cytogenetic analysis using monoclonal antibodies to human leucocyte common antigen, to human vimentin and to muscle actin. The immunoreactivity was positive for actin in 70–80% of the cells; 100% of the cells were positive for vimentin and all cells were ALC negative. These results indicated that the chromosomal abnormalities are present in the smooth muscle cells of the plaque. The hypothesis is proposed that the proliferation leading to the atherosclerotic lesion may primarily represent a hyperplastic response to mechanical and biological injuries and that this reactive proliferation is, in turn, associated with a tendency to chromosome instability.

Monosomy 7 is frequent in acute myeloid leukaemia (AML) and in preleukaemic dysmyelopoietic syndromes but often it is not the only chromosome anomaly associated with these conditions. We report 14 patients with “pure” monosomy 7 and their clinical and haematological data are analysed in order to clarify the possible implications of this chromosome anomaly. The following points are considered:1)In spite of the apparent variability of clinical forms in which monosomy 7 is found, several characteristics are common to all monosomy 7 patients, i.e. the presence of a preleukaemic phase and blood and marrow features suggesting the early involvement in the disease of all marrow cell lines. The different diagnoses associated with monosomy 7 are correlated with different steps of a unique myeloproliferative disease whose typical course can be reconstructed.2)Monosomy 7 has a negative prognostic value. When it is found in a preleukaemic disorder it indicates a high risk of progression to AML, while in AML it implies recurrent infections poor response to therapy and short survival.3)The significance of the lack of Colton blood group antigens in monosomy 7 patients is discussed, with particular regard to the fact that the patients in whom this lack was found are the only ones who had not received transfusions in the months before the tests were done.4)The finding of defective neutrophil chemotaxis in monosomy 7 patients is confirmed and the clinical importance of this fact is emphasized.5)The data on the 14 patients support the opinion that AML, in general, is heterogeneous in origin. It is postulated that monosomy 7 is a marker of a specific pathogenetic pathway of AML, which implies the beginning of the malignancy in a pluripotent stem cell.

A patient with chronic myelocytic leukaemia (CML) had the Philadelphia chromosome from the standard 9/22 translocation, a partial trisomy 1 secondary to an unbalanced 1/17 translocation, and a more recent clone with the addition of trisomy 22. This is the third case of partial trisomy 1 associated with the Philadelphia chromosome. Trisomy 1 in haematological disorders is discussed with reference to its clinical significance in CML, the segment of chromosome no. 1 involved, and the mechanisms of origin of the partial trisomies. Anomalies of chromosome 1, although not specific to any of them, seem to be important in the development of myeloproliferative disorders and of neoplasms in general.

A female with chronic myelocytic leukemia (CML) in blastic phase (BP) showed a masked Ph chromosome that had originated by a translocation between chromosomes 8 and 22, with no obvious involvement of chromosome 9. A duplication of the masked Ph and trisomy 13 were present as additional anomalies. The karyotype on peripheral blood unstimulated cultures was 48,XX,t(8;22)(p12;q11),+13,+der(22) t(8;22)/47,XX,t(8;22)(p12;q11),+der(22)t(8;22). While the duplication of the Ph is a frequent finding in BP of CML, we did not find any other case in the literature with duplication of a masked Ph. In situ hybridization with c-abl and bcr probes showed that a 3' bcr sequence was translocated to the der(8) chromosome, while the c-abl oncogene was transposed to the masked Ph.

An isochromosome (17q) may be observed in myelo-and lymphoproliferative disorders, as well as in solid tumours and it is very frequent in Ph1-positive chronic myelocytic leukaemia (CML) during the blastic phase. A study on the mechanism of origin and on the centromeric function of the i(17q)s was performed by means of the C- and Cd-staining techniques in four CML patients. In all these cases, as well as in four others reported in the literature, the i(17q) is dicentric thus indicating that its origin is due to a break on the short arms followed by joining of the two chromatids containing the centromere. The Cd-technique indicates that one of the two centromeres is inactive: this result is consistent with the fact that the i(17q) in CML is a step in the clonal evolution towards the acute phase.