Chromosome analysis in two unusual malignant blood disorders presumably induced by benzene.

Two patients with presumably benzene-induced malignant blood disorders with preleukemic phases were cytogenetically monitored through the courses of their diseases. Patient 1, in addition to a familial chromosome translocation [t(3;16)], developed karyotypic abnormalities in 100% of the marrow cells, including two translocation: t(9;16)] and t(4;15). Monosomy of chromosome 7 characterized the cells of patient 2. Cytogenetic monitoring of the patients at various phases of their diseases served as an important indicator of the transformation or progression of the preleukemia into frank leukemia and of the unusual behavior of such leukemic cells.     

Transformation of polycythemia vera to myelofibrosis and late appearance of a 5q— Chromosome anomaly

A characteristic 5 q− interstitial deletion was found to occur late during the course of the disease in three patients with polycythemia vera, and accompanied the transformation to myelofibrosis and the appearance of a preleukemic disorder.     

Chromosome 1p Abnormalities in B Non Hodgkin's Lymphoma

Thirteen patients with B-non Hodgkin's lymphoma and abnormalities of the short arm of chromosome 1 were evaluated, to see if this cytogenetic anomaly was associated with a particular subgroup of lymphomas. Large cell lymphoma was found in seven patients (with an immunoblastic component in four cases). Six patients with diffuse small cleaved cell lymphoma of non follicle centre cell origin formed a second group. The chromosome 1 breakpoints in the second group were located between p34 and p36, suggesting that genes located here may be important in the initiation or progression of these lymphomas.     

DNA methylation of phosphatase and actin regulator 3 detects colorectal cancer in stool and complements FIT

Using a bioinformatics-based strategy, we set out to identify hypermethylated genes that could serve as biomarkers for early detection of colorectal cancer (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical Test (FIT) was evaluated. Candidate genes were selected by applying cluster alignment and computational analysis of promoter regions to microarray-expression data of colorectal adenomas and carcinomas. DNA methylation was measured by quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole stool samples from in total 193 subjects, including 19 with advanced adenoma and 66 with CRC. For a large proportion of these series, methylation data for GATA4 and OSMR were available for comparison. The complementary value to FIT was measured in stool subsamples from 92 subjects including 44 with advanced adenoma or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel hypermethylated gene showing more than 70-fold increased DNA methylation levels in advanced neoplasia compared with normal colon mucosa. In a stool training set, PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33-75) for CRC and a specificity of 95% (95% CI: 87-98). In a stool validation set, sensitivity reached 66% (95% CI: 50-79) for CRC and 32% (95% CI: 14-57) for advanced adenomas at a specificity of 100% (95% CI: 86-100). Adding PHACTR3 methylation to FIT increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in CRC with a good performance in stool DNA testing and has complementary value to FIT.     

Simultaneous occurrence of myelodysplastic syndrome and monoclonal B lymphocytes with a different clonal origin

Bone marrow and peripheral blood from a myelodysplastic syndrome patient with trisomy 13 and monoclonal B lymphocytes (without evidence of systemic lymphoma) were investigated for clonal lymphoid lineage involvement using interphase fluorescence in situ hybridization (FISH) and X-chromosome inactivation assay (HUMARA) on CD19+ and CD34+ sorted cells. Trisomy 13 was detected in 55% of CD34+ cells and in 5.5% of CD19+ cells, the latter being comparable to the negative control specimen. X-chromosome inactivation showed both CD34+ and CD19+ cells to be monoclonal, though their inactivated X-chromosome was different. The results strongly suggested that both populations of CD34+ and CD19+ cells have originated from a different progenitor stem cell.     

Chromosome abnormalities in acute promyelocytic leukemia (APL).

Sixteen patients, 15 adults and one child, with APL have been studied cytogenetically; 14 of these had an abnormal karyotype (87%). Eleven of these consistently showed a t(15;17)(q26;q22) structural anomaly, one patient showed a 47,+8 karyotype, one a rearrangement of chromosomes No. 15 and No. 17, apparently different from that in the other patients, and one a No. 17 deletion without a demonstrable translocation. as an additional chromosome change trisomy No. 8 was found in 5 cases and monosomy No. 7 in two. The t)15;17)(q26;q22) structural anomaly is highly characteristic of APL, is found in APL of children and adults, but it is apparently not associated with a clinically different form of APL.     

Variant translocation t(15q;17q) accompanying a promyelocytic accelerated phase of Ph-positive chronic myeloid leukemia

One case of Philadelphia-positive chronic myeloid leukemia showed a high promyelocytic component associated with a variant t(15q-,17q+) translocation. A key role for chromosome #17 in the promyelocytic proliferation and/or differentiation is emphasized.