Inherited aplastic anemia with abnormal clones in bone marrow and increased endoreduplication in peripheral lymphocytes

Cytogenetic studies in peripheral blood and bone marrow cells from a female patient (aged 31 years) with inherited aplastic anemia and without other congenital anomalies are reported. Endoreduplication was increased in stimulated peripheral lymphocytes in several investigations. Chromosome breaks were shown to be near the control frequency, although chromatid exchange figures and dicentrics were present. Cytogenetic analysis was extended to the three children of our patient. Abnormal clones were detected in bone marrow preparations of our patient in all cytogenetic investigations. At the first examination, two of these clones were prevalent, with their karyotypes being 48,XX,+9,+16 and 46,XX,dup(1)(q24→q32),t(17;?)(p12–13;?). The prevailing karyotype after 2 years was 46,XX,t(17;?)(p12–13;?). Involvement of chromosomes #1 and #17 is discussed, taking into account data from the literature concerning several human neoplasias.     

Chromosomal alterations in the course of viral leukemogenesis in the rat

A cytogenetic study of 35 primary thymic lymphomas induced in rats by the Gross leukemia virus revealed the presence of widespread aneuploidies, ranging from cells with 35 chromosomes or less to triploid and tetraploid cells. Analysis by G banding revealed that chromosomes No. 1, 2, 9, 12, 18–20, X in females, and Y in males were lost preferentially; unidentified marker chromosomes of various morphology and length were present in a high percentage of aneuploid mitoses. Similar alterations were observed in preleukemic thymi from rats sacrificed 30 days after virus injection, when clinical or histologic signs of the disease had not yet appeared. In rats that were sacrificed 7 or 15 days after virus injection, chromosomal anomalies were much more limited, although significantly more abundant than in the controls. Rats that were free of tumor at 130–160 days after virus injection showed a regression of the chromosomal anomalies, suggesting that these are not irreversible and are not necessarily followed by the development of a lymphoma.     

Cytogenetically distinct leukemic cell lines displaying in vitro specific proliferative and differentiation capacities may account for early disease relapse in the blast phase of CML

The cytogenetic features and the proliferative and differentiation capabilities of blast cell fractions purified on a density gradient were studied in one patient with chronic myeloid leukemia (CML) in blast crisis, both at the emergence and at relapse of the disease. The results show that relapse was due to the appearance of a new leukemic cell line that was characterized by peculiar chromosomal, growth, and differentiation features, which seemingly accounted for early refractoriness to therapy and disease progression.     

21q− in primary thrombocythemia

In 11 of 18 patients with primary thrombocythemia (PT), karyotype analysis of marrow cells after Giemsa chromosome banding revealed a previously unrecognized specific abnormality, consisting in a deletion of the long arm of a chromosome #21 (21q?), del 21(q21). This deletion was observed in 11.1 to 47.6% of marrow cell metaphases. In 8 patients, 21q? cells were detected prior to any therapy. In 3 other patients, 21q? cells were found during relapse after busulfan therapy. In one patient, a translocation of the deleted material on the long arm of a #11, t(11;21)(q25;q21), was observed.     

Malignant melanoma: sister chromatid exchange analysis in three families

Sister chromatid exchange (SCE) was analyzed in stimulated lymphocytes and skin fibroblasts in members of three families with cutaneous malignant melanoma (CMM). Two of these families were characterized by familial CMM; the other family had one patient affected by CMM and two others with other cutaneous melanocytic lesions. All the patients had undergone surgery but no chemotherapy. Higher and differing SCE rates were found in lymphocytes and in fibroblasts of all patients. A wide range of SCE distribution was found in patients with high SCE rate. A few healthy close relatives also showed relatively high SCE rates and wide range distributions. These subjects may be regarded as a subset of family members at high risk for developing cancer. The variability of SCE rates and distribution may reflect genetic heterogeneity of CMM.     

Derivative 11 marker chromosome in bladder carcinoma

Cytogenetic studies on bladder carcinomas from two patients were carried out on preparations obtained by a direct method. The chromosome mode was 49 and 55, respectively. Several karyotypic changes were found in the tumors. Moreover, the analysis of Q-banded chromosomes revealed the presence in both cases of a chromosome 11p+. These rearranged chromosomes showed a very similar banding pattern. The finding of a der(11) chromosome marker in two patients is intriguing, and suggests the possibility of nonrandom chromosome changes in bladder carcinoma, as already found in other kinds of tumors. The occurrence of chromosome #11 aberrations in tumors of the urinary tract is discussed in connection with the current theories on oncogenesis.     

Karyotype evolution in a case of chronic myelogenous leukemia with an unusual Philadelphia chromosome translocation,t(4;22), and an additional translocation,t(3;5)

A patient with chronic myelogenous leukemia was found, at the time of diagnosis, to have an unusual Philadelphia chromosome translocation, t(4;22) (q35;q11) and an additional previously unreported translocation, t(3;5) (q27;q22). The blastic crisis, which occurred after 14 months, was characterized by the appearance of i(17q). Ten months later, two different hyperdiploid cell lines with 50 chromosomes were found in about 20% of the metaphases examined.     

Sister chromatid exchanges induced by nitrogen mustard in Fanconi's anemia. Application to the detection of heterozygotes and interpretation of the results

Nitrogen mustard-induced SCE were studied on Fanconi's anemia (FA) patients, FA parents, and control lymphocyte cultures. When low doses of nitrogen mustard were added at the time cultures were initiated, a distinction could be made between FA heterozygotes and controls. In FA heterozygotes increase of SCE levels higher than that observed in controls was found, thus allowing the recognition of heterozygotes. FA cells appeared to be more sensitive to nitrogen mustard than FA heterozygous and control cells. The data argues in favor of an excision-repair defect, and is discussed in the light of possible repair and SCE production mechanisms.     

A 14q+ chromosome in a malignant lymphoma in a patient with Down's syndrome

A 17-year-old Japanese boy with Down's syndrome developed leukemic lymphosarcoma; histology of a lymph node biopsy revealed a malignant lymphoma, of the poorly differentiated lymphocytic (ML-PDL) or possibly lymphoblastic type (ML-LB). The Giemsa-banding technique for chromosome analysis revealed the karyotype of the lymphoma cells to be 47,XY,+21,14q+. A chromosome study of PHA-stimulated lymphocytes showed a 21-trisomic pattern, i.e., 47,XY,+21. The 14q+ marker was a product of a translocation in which the long arm of chromosome No. 8 (probable break at band q11) was translocated to the long arm of a No. 14 at band q32, which is a region usually affected in various types of lymphomas. Two normal No. 8 chromosomes were present. Thus, the lymphoma cells were partially trisomic for chromosome No. 8.     

Masked Philadelphia chromosome caused by translocation (9;11;22)

In a patient with chronic myelocytic leukemia (CML), chromosome analysis revealed a translocation involving chromosomes No. 9, 11, and 22, with three break points, thus giving origin to a so-called "masked" Philadelphia chromosome (Ph1). A review of similar cases reported in the literature indicates that a masked Ph1 is very rare, that the chromosomes involved vary from case to case, and that in most cases the pattern of the rearrangement is quite different from that of two- and three-chromosome variant Ph1 translocations.     

Absence of heteromorphism of chromosome #2 homologues in patients with hereditary adenomatosis of the colon and rectum

Measurement analysis of lymphocyte prometaphase chromosomes from three patients with hereditary adenomatosis of the colon and rectum could not confirm the heteromorphism of chromosome #2 homologues, which was suggested by Gardner et al. Instead, the analysis showed to what extent individual homologous pairs are "heteromorphic" quantitatively.     

Isochromosome (17q) in Philadelphia chromosome (Ph1)-negative juvenile chronic myelocytic leukemia

A dicentric isochromosome of the long arm of one chromosome #17 was the only abnormality present in a 12-year-old boy with Philadelphia chromosome (Ph¹)-negative juvenile chronic myelocytic leukemia. This association does not seem to have been reported in the literature. It is postulated that the finding of an isochromosome (17q) may also have a negative prognostic value in the Ph¹-negative type of chronic myelogenous leukemia.     

A current view of the human Ia system based on serological and immunochemical analysis

We have approached the analysis of the human Ia system by localizing antigenic determinants on subsets of Class II molecules. For this purpose two classes of reagents have been used: alloantisera and mouse anti human monoclonal antibodies (moabs). We summarize here the most recent data obtained by these two approaches.     

Acute nonlymphocytic leukemias and dysmyelopoietic syndromes in patients treated for Hodgkin's lymphoma

The clinical, hematological, and cytogenetical features of six patients with hematological disorders secondary to Hodgkin's lymphoma (HL), are described. Three patients developed a dysmyelopoietic syndrome (DMS); three, an acute nonlymphocytic leukemia (ANLL). Chromosomal analyses showed a normal karyotype in one case and an abnormal one in five cases: one with a 53-chromosome clone, two with a pseudodiploid pattern plus hyperdiploid subclones, and two with a hypodiploid pattern. Trisomy 21 was observed in two cases, tetrasomy 21 in one case, monosomy 5 and monosomy 7 in two cases. The correlations of chromosomal changes with hematological abnormalities or clinical aspects are discussed.     

Chromosome number 11 and Wilms' tumor

Cytogenetic studies have been carried out on cells derived from two Wilms' tumors in vitro. Both tumors had a diploid chromosome range. One tumor was shown to have a definite stemline; 46,XY,4p+,del(9)(q22),11p?q?,11p+, and the other a range of variation chiefly involving chromosomes No. 11, 4, 7, and 2; most changes in chromosome No. 11 took the form of deletions of the short arm.High resolution chromosome analysis of peripheral blood lymphocytes of the two patients revealed apparently normal karyotypes. These findings suggest that changes in the short arm of chromosome No. 11 are important in the development of Wilms' tumor in normal individuals. This association is reinforced by the fact that patients with spontaneous aniridia with a 1 in 3 risk of Wilms' tumor have been reported as having a specific 11p13 deletion.     

Translocation involving chromosome 22 in Ewing's Sarcoma. A cytogenetic study of four fresh tumors

Ewing's sarcoma was described in 1921 by James Ewing as a diffuse endothelioma of bone and, for some time, was believed to be an undifferenciated type of Parker's sarcoma. At present, these two entities are thought to be distinct, the macroscopic and microscopic aspects of Ewing's sarcoma being very characteristic, although the exact cell type of this tumor remains unknown. This has lead many workers to study this sarcoma in order to recognize its origin.We thought it of interest to carry out cytogenetic investigations of our cases of Ewing's sarcoma, since very few chromosomal data on this malignancy exist in the literature [1–3].     

Nitrogen mustard-induced chromosome breakage: A tool for Fanconi's anemia diagnosis

Chromosome studies were performed on phytohemagglutinin-stimulated lymphocytes from 9 Fanconi's anemia (FA) patients, 6 of their parents, 7 controls, 2 children with aplastic anemia of unknown etiology, and one child with Zinsser-Cole-Engman syndrome. The addition of low doses (0.0085 μg/ml) of nitrogen mustard to cultures dramatically increased the chromosome breakage level in FA, the increase evaluated from means of chromosome anomalies per cell was highly significant (p < 0.001). On the other hand, the means of chromosome anomalies per cell increased greatly only at higher dilutions in all non-FA subjects. The high susceptibility of FA cells to chromosome breakage by nitrogen mustard may be of use as a diagnostic test and might be useful for prenatal detection of the disease.     

Secondary chromosome changes in chronic myeloid leukemia: Relation to treatment

Thirty four patients with Philadelphia (Ph¹) chromosome positive chronic myeloid leukemia with clonal bone marrow chromosome aberrations in addition to the Ph¹, were divided into two groups: 1) 23 patients treated with busulfan only during the chronic phase, and 2) 11 patients treated with intensive chemotherapeutic schedules during the chronic phase. In all the material studied, about 85% of the patients showed at least one of three particular changes: +8, iso(17q), and/or +Ph¹. The frequency of each of these three aberrations was similar in the two groups. Additional structural changes of a clonal nature were, however, seen in only 3 of the 23 patients treated with busulfan only, but were present in 5 of the 11 patients treated with intensive chemotherapy. The results indicate that intensive chemotherapy may produce new stable abnormal clones in patients with leukemia. Furthermore, chromosome 1 was involved in aberrations in all 5 patients with structural changes undergoing intensive chemotherapy, but in no patient treated with busulfan only. The 11 patients treated with intensive chemotherapy were studied in Italy, whereas 20 of the 23 patients treated with busulfan only were studied in Sweden. The possibility that the differences recorded between the two groups may be geographical in nature rather than induced by treatment cannot be excluded.