P. Carbone

Chromosomal abnormalities in Waldenström's macroglobulinemia

We report the results of cytogenetic studies of direct bone marrow (BM) preparations and of short-term BM and peripheral blood (PB) cultures from 17 patients with Waldenströms macroglobulinemia. We noted clonal chromosome changes in 10 patients. Abnormalities affected chromosomes X, Y, 2, 4, 5, 15, 16, 18, 19, 20, 21, and 22; in particular, chromosomes 2, 4, and 5 were involved in structural changes: a homogeneously staining region [hsr(2)], a der(4)t(4;?)(q32;?), and a 5q+. The other chromosomes were involved in numerical abnormalities, such as pseudodiploidy (a 46,X, -X, + 15 clone), loss of chromosome Y, and monosomy of chromosomes 16, 18, 19, 20, 21, and 22. Nonclonal chromosome rearrangements were also observed. The results are discussed in comparison with the few data reported in the literature, and the finding of an hsr in the long arm of chromosome 2 is emphasized; indeed, this is the first report of hsr in WM.

Cytogenetic studies in five patients with myelofibrosis and myeloid metaplasia.

Chromosome studies of five patients with myelofibrosis and myeloid metaplasia were carried out on bone marrow cells and/or on peripheral blood without PHA. Abnormal clones were found in three patients. Such clones were a minority, compared with the number of cells with normal karyotypes in all three patients. Chromosomes abnormalities consisted of 5q- (case 5), 13q- (case 2), and a small supernumerary acrocentric marker (case 3). One of our five patients, a woman aged 75 (case 1), showed a constitutional karyotype 46,XX,inv(5)( p15q11 ). The same chromosome rearrangement was present in 100% of the stimulated peripheral lymphocytes of this patient and in one of her sons with a normal phenotype. One patient (case 4) had a normal karyotype. These results are discussed and compared with data from the literature concerning myelofibrosis and other myeloproliferative diseases.

Translocation t(8;16)(p11;p13) in acute nonlymphoblastic leukemia (M4) possibly secondary to Hodgkin's disease

Simultaneous involvement of bands 8p11 and 16p13 in a primary, even though rare, chromosomal translocation recently described in acute nonlymphocytic leukemia may be of crucial interest in some subtypes of this acute leukemia, particularly in the monocytic form. In the present report we describe this translocation in acute nonlymphoblastic leukemia FAB M4, possibly secondary to Hodgkins disease, though it is also possible that the leukemia may have developed de novo. The aberration t(8;16)(p11;p13) was present in 100% of direct and cultured bone marrow cell preparations. A very high frequency of cells with nonclonal structural chromosome aberrations was also observed in peripheral blood cultures (more than 53%). Random translocations and deletions constituted most of the observed alterations. These findings are discussed with regard to the relationships between secondary leukemias and intensive polychemotherapeutic treatments of primary neoplasias.

Cytogenetic findings in secondary acute nonlymphocytic leukemia

We have report the results of cytogenetic studies carried out in eight patients with acute nonlymphocytic leukemia developed after primary neoplasias. In seven of the reported cases, clonal chromosome aberrations were found, some being specific of de novo acute nonlymphocytic leukemia (ANLL). Numerical abnormalities were detected, such as the total monosomy of chromosomes 5, 7, 21, trisomy of chromosomes 8, 11, 15, and duplication of chromosome Y. Structural changes were also observed: a del(12)(p12), a del(16)(q22), the translocations t(3;5)(p21;q35),t(3;7)(p21;q35), and t(12;14)(p12;q32) and other changes involving chromosome 8. The finding of a hypertetraploid karyotype with complex structural chromosome aberrations in a patient with erythroleukemia, developed after non-Hodgkins lymphoma, is of particular interest. Data reported in this work are discussed with regard to the relationship between secondary and de novo ANLL and the finding of chromosome aberrations other than total or partial monosomy of chromosomes 5 and 7 is emphasized.

Complex translocation t(3;9;22) and paracentric inversion of chromosome 3 in blastic crisis of chronic myeloid leukemia

We report a complex rearrangement observed in both the short and long arms of chromosome #3 in a patient with Ph-positive chronic myeloid leukemia in blastic crisis and without thrombopoietic abnormalities. The rearrangement consisted of a complex translocation, t(3;9;22)(p21;q34;q11), and a paracentric inversion of the long arm of the same chromosome #3 involved in the translocation. Involvement of chromosome #3 in complex translocations in chronic myeloid leukemia and the relationship between 3q anomalies and thrombopoietic diseases are discussed.

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.

Clastogenic and aneuploidizing effects of antiblastic busulphan revealed by kinetochore immunofluorescence in CHO cells

We utilized, in CHO cells, the cytoplasm preservation technique to evaluate the micronucleus frequency at different busulphan concentrations, and the indirect immunofluorescence technique, using sera obtained from patients with scleroderma (CREST variant), to analyze if busulphan-induced micronuclei have kinetochores. Results show that this alkylating agent is capable of causing a significant increase of micronuclei in vitro, a great part (40%) of them having CREST-positive kinetochores. These findings confirm the clastogenic effect of busulphan and reveal a considerable capability of this agent to induce aneuploidy. These results are examined taking into account the high incidence of secondary neoplasias induced by chemotherapy with alkylating agents utilized against primary neoplasias.

Low Epichlorohydrin Concentrations Induce Sister Chromatid Exchanges in Human Lymphocytes «in Vitro»

SUMMARYSister chromatid exchange (SCE) frequencies in « in vitro » cultures of human lymphocytes were analysed after exposure to non toxic concentrations of epichlorohydrin (1×10−5M, 1×10−8, 1×10−11M). High sensitivity of SCE test allowed to point out a gradual increase of SCE frequency. In particular, 1× 10−8M ECHH, which had proved unable to increase the frequency of structural chromosome aberrations, was indeed able to induce a significant increase of SCE.

Translocation t(8;14)(q24;q32) and del(1)(p22) in FAB-L1 adult acute lymphoblastic leukemia with long survival

Clonal chromosome changes were found in a patient with FAB-L1 acute lymphoblastic leukemia. The changes consisted of a t(8;14)(q24;q32), Burkitt type, and a rare marker chromosome 1p-. The breakpoint in this chromosome was localized at band 1p22. Both these abnormalities were present in 100% of unstimulated peripheral blood cells. The detection of the t(8;14) in a case of acute lymphoblastic leukemia, without a clear evidence of B immunophenotype and with an unusual long survival (more than 3 years), is discussed.

t(1 ;2), inv(1) and Trisomy 1q during the Blastic Phase of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

Several karyotype changes observed during the blastic phase in 2 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) are reported. Rearrangements involving chromosome 1, i.e., translocations, a pericentric inversion and trisomies of its long arm, are described. In the first patient whose chronic phase was very long (17 years), the uncommon association between i(17q) and Ph duplication has been observed during the blastic phase, beside the involvement of chromosome 1. In the second patient, additional abnormalities involving chromosomes 1, 2, 4, 8, 18 and 21 were present. Of particular interest is the finding of a t(1;2). In this case, the presence of hyperdiploid cells with 49-50 chromosomes, prevailing at the blastic crisis, was due to the evolution of the hypodiploid clone with the 45,XX,t(9;22),-21 karyotype found during the chronic phase. The occurrence of chromosomal changes involving chromosome 1 during the blastic phase of CML is emphasized.