Increased karyotype precision using fluorescence in situ hybridization and spectral karyotyping in patients with myeloid malignancies.

We studied seven patients with various malignant hematologic disorders using fluorescence in situ hybridization (FISH) and one of these patients with spectral karyotyping (SKY). With appropriate probes, the t(8;21) and inv(16) were confirmed in two patients and the karyotypic precision was increased in five others using FISH and SKY. Two of three patients with 12p rearrangements had a deletion of one TEL allele. Thus, these newer techniques are an important adjunct to accurate chromosome analysis in malignancy.

MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia.

We describe a patient with acute myeloblastic leukemia (AML-M0) whose cells had a t(2;11)(p21;q23). Fluorescence in situ hybridization analysis with a probe for MLL showed that it was split, hybridizing to both the derivative 2 and 11 chromosomes. Nineteen other patients with 2p;11q translocations have been described; breakpoints in 14 of these are the same as in the case we describe. The phenotype of these patients is quite variable, with 14 patients having myelodysplastic syndrome which evolved to AML in six. Four patients had AML and two had acute lymphoblastic leukemia. MLL status has been studied in two other patients; one had MLL rearranged and one did not.

[Karyotypic anomalies and chromosomal sites of increased fragility in colorectal cancer]. / Anomalii kariotipa i saity povyshennoi lomskiti khromosom pri kolorektal'nykh rakakh.

Karyotypic structural aberrations in tumor cells and chromosome constitutive fragile sites (cFSs) in peripheral blood lymphocytes were studied in ten patients with colorectal adenocarcinoma Most chromosome breakpoints (38 out of 40, i.e., 95.0%) were shown to be located within cFSs in tumor cells. Expression of 24 out of 137 cFSs in patients was higher than that in healthy donors. Four of these cFSs (6q26, 7q36, 16q23, and 17q21), were involved in the formation of nonrandom tumor cell chromosome markers most characteristic of colorectal neoplasms. The frequency of damages induced within these sites was analyzed in each patient. Expression of 7q36, 16q23, and 17q21 was increased in blood cells of patients carrying specific chromosome rearrangements with the breakpoints within these sites. The association between nonrandom chromosome aberrations in tumor cells and cFSs in normal cells is discussed.

[Geographic differences in the frequency of chromosome alterations characteristic of cancer of the large intestine]. / Geograficheskie razlichiia v chastote khromosomnykh izmenenii kharakternykh dlia raka tolstoi kishki.

The authors' material (33 tumours) and that from foreign literature (18 to 100 tumours from every country) was used. The following chromosome aberrations were compared: the deletion of a part of chromosome 1 short arm, deletion of chromosome 5 and a part of its long arm, additional chromosomes 7, complete or partial deletion of chromosome 17 short arm, deletion of chromosome 18 and appearance of additional chromosomes 20. Clear-cut differences were revealed between the following three groups of regions: 1) countries of the Eastern and Western Europe (Russia, France, Germany); 2) Northern Europe countries (Denmark, SWeden); 3) USA and China. Geographical differences in chromosome anomalies in hemoblastosis were found in 1970s, the difference in colon carcinoma are presented for the first time. The experimental results suggest that non-homogeneous distribution of the karyotype alterations typical for certain morphological types of malignant tumours are due to different environmental influences.

Translocation (2;3)(p13;q26) in two cases of myeloid malignancies. Acute myeloblastic leukemia (M2) and blastic phase of chronic myeloid leukemia.

Two cases of myeloid leukemias (acute [AML M2] and chronic [CMC]), blastic crisis, with identical t(2;3)(p13;q26) are described. These cases had some peculiarities: no significant decrease of blood thrombocyte count in the AML patient and high increase of blood thrombocyte count during blastic phase in the CML patient; dysplastic megakaryocytes in bone marrow and unfavorable course of the disease; and short remission (3 months) in AML and short chronic phase (8 months) in CML. Clinical and morphologic findings in patients with t(2;3)(p13;q26) resembled those in cases with 3q21q26 syndrome or with other chromosome rearrangements involving 3q21 or 3q26.

[Megakaryocytic dysplasia in acute nonlymphoblastic leukemias]. / Displaziia megakariotsitov pri ostrykh nelimfoblastnykh leikozakh.

Megakaryocytic dysplasia, platelet and megakaryocytic counts were measured in 87 ANLL patients. High megakaryocytic levels were registered in 16.1%, normal in 17.2%, low or negligible in the rest of the examinees. Half of the patients had dysplasia. Thrombocytopenia present in 93% of cases attested to ineffective proliferation of megakaryocytes. Increased number of megakaryocytes with signs of dysplasia occurred more commonly in M0- and M4- variants of ANLL universally in anomalies of chromosome 3 long arm with involvement of q21 and/or q26 segments and occasionally in combination with other chromosome disorders. Megakaryocytosis developed less frequently in patients with ANLL variant M2 with t (8;21) and did not correlate with granulocyte and erythroid cell dysplasia. Pronounced megakaryocytosis in combination with thrombocytosis emerged in 4 patients: 2 of them had typical anomalies of chromosome 3--inv3(q21q26) and dup (3q21q26), 1 had monosomy 7 and 1 normal karyotype. Potential mechanisms responsible for dysplasia of megakaryocytes in ANLL are considered.

[Nonrandom karyotype changes in chemically induced tumors of the Djungarian hamster]. / Nesluchainye izmeneniia kariotipa v khimicheski indutsirovannykh opukholiakh dzhungarskogo khomiachka.

In the cells of tumors induced with methylcholanthrene in wild type and mutant (pink-eyed dilution) Djungarian hamsters non-random involvement in structural changes of certain chromosomes (Xp, 3p and 3q, 7q, 8q) was revealed. In addition, characteristic feature of the majority of tumors was varied number of double-minutes chromosomes (DMs). In some tumors, the markers with long homogeneously or differentially stained regions (HSRs and DSRs) were also present. The DMs, HSRs and DSRs are known as the structures containing amplified genes.

[Sensitivity of grey and beige Djungarian hamsters to the blastomogenic action of 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene]. / Chuvstvitel'nost' serykh i bezhevykh dzhungarskikh khomiachkov k blastomogennomu deistviiu 7,12-dimetilbenz(a)antratsena i 3-metilkholantrena.

Sensitivity of normal gray and mutant beige (pink-eyed dilution mutation) Djungarian hamsters to the carcinogenic activity of 7,12-dimethylbenz (a) anthracene (DMBA) and 3-methylcholanthrene (MC) was studied. No differences between these two groups of animals which were given pills with DMBA were revealed. At the same time the beige females were found to be more sensitive to MC than males and hamsters of wild (gray) colour. Among tumours induced both by DMBA and MC fibrosarcomas prevailed both in the gray and beige hamsters. Fibrous histiocytomas were detected only in the MC-infected hamsters. Epithelial tumours were found only in females.

Chromosomes in acute leukemia.

The karyotype of leukemic cells of 78 acute leukemia patients (37 ANLL, 34ALL, and 7 of unknown type) was studied by means of G-banding. Chromosomal abnormalities were found in 50 patients (72%). Chromosomes 8,21,5,7,11, and 19 were preferentially involved in the abnormalities, both in ANLL and in ALL. A high incidence of the characteristic rearrangement t(8;21) was noted in AML: (in 6 of 22 AMP patients). An identical reciprocal translocation--t(4;11)--was seen in 4 out of 34 ALL patients.

Chromosomal marker 20q- in cases of osteomyelosclerosis and CML.

Two male patients with myeloproliferative disorders (osteomyelosclerosis in one and CML in the other) were found to have a chromosomal marker 20q- in blood cells (unstimulated short time cultures). Marked erythropoietic disturbances were not revealed in these cases. The specificity of the 20q- marker for red cell disorders is discussed.

[Karyotypic analysis of human cell lines (CaVe and HeLa) by the method of differential staining of chromosomes]. / Analiz kariotipa nekotorykh linii kletok cheloveka s pomoshch'iu differentsial'noi okraski khromosom linii CaVe i HeLa

Karyological analysis of CaVe (human stomach cancer) and HeLa cell lines was carried out by means of differential Giemsa staining. In the CaVe cells 12 marker chromosomes were revealed, seven of them similar to those found in our HeLa cell strain. Four markers in our HeLa subline and seven in CaVe cells were similar to those of HeLa sublines described in literature. The authors have arrived at the conclusion that the CaVe line isolated in 1961 was contaminated and now represents a variant of HeLa cell line.