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G W Dewald

Publications and source records attributed to G W Dewald.

121 records · Page 7Linked to original sources

Chromosome abnormalities in malignant hematologic disorders.

Certain chromosome abnormalities have been detected in routine cytogenetic studies of patients with hematologic disorders. This article is a cytogenetic and clinical review of 28 structural and 15 numeric chromosome abnormalities. As a group, the structural abnormalities involved 40 different chromosome breakpoints and included 13 types of translocations, 8 deletions, 3 isochromosomes, 3 inversions, and 1 duplication. The numeric abnormalities included 4 types of monosomy, 10 trisomies, and a near-haploid category. We determined the relative frequency for each of these anomalies in our practice by reviewing the results of 1,228 consecutive specimens studied between 1979 and 1984 in which a chromosomally abnormal clone was found; 61% of these specimens had one or more of the selected anomalies. The three most common translocations were 9;22 translocations (378 specimens), 8;21 translocations (15 specimens), and unbalanced abnormalities derived from 1;7 translocations (13 specimens). The two most common deletions were those involving the long arm of chromosomes 5 (101 specimens) and 20 (65 specimens). The most common isochromosome was i(17q) (33 specimens). The two most common types of monosomy were loss of a Y chromosome (118 specimens) and monosomy 7 (97 specimens). The three most common trisomies were + 8 (161 specimens), +21 (53 specimens), and +19 (31 specimens). Each of the 43 anomalies was observed in patients with different types of hematologic disorders, but in most cases one kind of neoplasm usually predominated.

Chromosome Aberrations↗

The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

Amyloidosis↗

Clinical characteristics and prognosis of 50 patients with a myeloproliferative syndrome and deletion of part of the long arm of chromosome 5.

Of 50 consecutive patients (30 female and 20 male; median age, 70 years) with a myeloproliferative disorder and a 5q- chromosome, 12 (24%) had refractory anemia, 16 (32%) had refractory anemia with excess blasts, 13 (26%) had acute nonlymphocytic leukemia, six (12%) had the 5q- syndrome, and three (6%) had an unclassifiable myeloproliferative disease. Twenty-five patients had only a 5q- anomaly (group 1), and 25 had a 5q- plus additional chromosome abnormalities (group 2). Four types of 5q- anomalies were recognized: a del(5)(q13q33) occurred in 39 patients, a del(5)(q31q35) in nine, a del(5)(q22q33) in one, and a del(5)(q13q35) in one. The survival distribution for patients in group 1 was significantly better (P = .012) than for those in group 2. Cox-model analyses indicated that having a 5q- chromosome and other abnormalities is significantly (P less than .01) associated with poor survival even after adjustment for the effects of other important factors such as type of disease, age, and sex. The two groups had similar distributions of most variables, including age, sex, and disease types. However, patients in group 1 had a significantly higher platelet count and mean corpuscular volume than those in group 2. Only two patients in group 1 had had prior chemotherapy, but nine in group 2 had had either prior chemotherapy or radiation or both, and one patient in group 2 had had heavy exposure to pesticides.

Adult↗

Hematologic manifestations associated with deletions of the long arm of chromosome 20.

We investigated 20 patients with hematologic disorders who had a clone of cells with a deletion of most of a chromosome #20 long arm (20q-) in the bone marrow. Three patients had polycythemia vera (PV), 6 had acute nonlymphocytic leukemia (ANLL), 8 had preleukemia (PL), and 3 had other myeloproliferative disorders. In our laboratory, a 20q- chromosome is found in 6% of patients with PV, 3% of patients with ANLL, and 1% of patients with PL. Among the 6 patients with ANLL and a 20q- abnormality, 3 had erythroleukemia. There were no apparent clinical differences among our patients with 20q- chromosomes compared with other patients with similar disorders who did not have a 20q- chromosome. The breakpoint of the 20q- anomaly, in each instance, was in band 20q11, but it occurred near the centromere at 20q1101 in 16 patients and at the distal part of this band at 20q1109 in 4 patients. Three of the 4 patients with a breakpoint at 20q1109 had PL.

Aged↗

Erythrophagocytic acute lymphocytic leukemia with B-cell markers and with a 20q- chromosome abnormality.

An erythrophagocytic neoplastic infiltration of the bone marrow which resembled malignant histiocytosis was found in an elderly man who, when initially examined, had fever and cytopenias. Results of cytochemical and immunologic studies were consistent with an acute lymphocytic leukemia in which the lymphoblasts showed the simultaneous expression of lymphoid stem cell and B-cell markers. Chromosome analysis revealed an abnormal clone with a deletion of part of the long arm of chromosome 20. This case illustrates (1) the occurrence of striking erythrophagocytosis by lymphoblasts at the time of initial presentation of a patient with acute lymphocytic leukemia, (2) the fact that abnormalities of chromosome 20 can occur in patients with acute lymphocytic leukemia, and (3) the capability of lymphoid malignant lesions to show the simultaneous expression of antigens that are characteristic of different stages of lymphoid differentiation.

Aged↗

A possible specific chromosome marker for monocytic leukemia: three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia.

An apparently balanced 9;11 reciprocal translocation with break points most likely at 9p22 and 11q24 was found in 3 patients with acute monocytic leukemia [M5 in the French-American-British (FAB) classification schema]. This translocation was not observed in 6 other patients with M5 acute nonlymphocytic leukemia (ANLL) or in chromosome studies on 143 patients with other types of ANLL. This study supports the previously published suggestion that such 9;11 translocations may be associated with some patients with M5 ANLL. In this report, we have also included a patient with M5 ANLL who had an 11;17 translocation with break points apparently at 11q24 and 17q21. Perhaps this is a variant translocation of chromosome No. 11, which may also be associated with monocytic leukemia.

Aged↗

Cytogenetic diagnosis of malignant pleural effusions: culture methods to supplement direct preparations in diagnosis.

Pleural effusions from 100 unselected patients were studied cytogenetically by direct preparation, 24- and 48-hour cultures, and long-term cultures. The study included benign pleural effusion in 17 patients, malignant pleural effusion in 76, and an indeterminate cause in 7. Two cytogenetic criteria for detecting a malignant lesion were tested: (1) three or more metaphases that were either hyperdiploid or had markers and (2) two or more metaphases with the same markers (clone). Among the malignant pleural effusions, 51 (67%) were positive by at least one method when the first criterion was used and 34 (45%) were positive by at least one method when the second criterion was used. By the first criterion, at least one of the culture methods was positive in 13 cases (17%) in which direct preparations were negative; there was 7 such cases (9%) by the second criterion. Apparently, culture methods alone are not better than direct preparations but are useful in supplementing direct preparations. There was one false-positive long-term culture by the first criterion. Thus, the clone criterion of malignancy may be more accurate but is less sensitive. There was no evidence that therapy had any effect on the cytogenetic studies.

Cells, Cultured↗

Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia.

Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA.

Adult↗

A tdic(5;15)(p31;p11) chromosome showing variation for constriction in the centromeric regions in a patient with the cri du chat syndrome.

Some dicentric chromosomes show only one primary constriction at metaphase and behave in cell division as if they are monocentric. The few previous reports of tdic (translocation dicentric) chromosomes showing one morphologic indicate that among the cells of an individual the same centromere consistently shows the primary constriction. The present case deals with a tdic(5;15)(p13;p11) chromosome that is an exception to this pattern. Scoring 98 GTG-, C-, and QFQ-banded metaphases specifically for primary constrictions revealed 15 (15%) containing a tdic chromosome with a single primary constriction. Among these chromosomes, 8 (8%) were at the chromosome 15 centromere and 7 (7%) were at the chromosome 5 centromere. The remaining 83 (85%) tdic chromosomes showed two primary constrictions. We analyzed a total of 172 metaphases from peripheral blood, and all except 3 (1.7%) contained the tdic chromosome. Among these three cells, the tdic chromosome was broken in two and absent in one, which indicates that there was some unstable separation of this dicentric in cell division. In two metaphases, there was a chromatid gap at the site of one centromere. Possibly, the absence of certain primary constrictions was associated with deletion of centromeres. This mechanism may be a continual source for additional centromere inactivation during the life of this patient. This case demonstrates that for some dicentrics either centromere may become nonfunctional and inactivation can occur more than once within an individual. The karyotype of this patient was 45,XX,tdic(5;15)(p31;p11). Thus, she was monosomic for about 3/4 of the chromosome 5 short arm. Clinically, this infant had a shrill catlike cry and facies of the cri du chat syndrome.

Centromere↗

Chromosomal studies in cryptorchidism.

The chromosomes of undescended tests from 13 boys were analyzed. In 12 of these patients the peripheral blood chromosomes were examined and in 7 the chromosomes of normal skin cultures were examined. In addition to standard techniques the chromosomes also were analyzed by G and Q-banding methods. We were unable to detect any significant abnormalities of either chromosome number of structure in the undescended testes. Thus, our investigation failed to demonstrate a chromosomal lesions that may be responsible for maldescent of the testes. Our investigation did not reveal any changes in the chromosomes of these undescended testes that could be interpreted as indicating a potentially malignant state.

Adolescent↗

A computer-based videodensitometric system for studying banded human chromosomes illustrated by the analysis of the normal morphology of chromosome 18.

A computer-based, high-resolution, high-speed system is described for the digitization of television images of human G-banded chromosomes, on-line directly from a microscope. The digitized data are processed by a computer to determine the total length and centromere index of individual chromosomes and to obtain an integrated density profile representing the band pattern. The density profile is reduced by the computer to a series of dark and light bands, each with a defined position, width, and density. The results are displayed by the computer on a television monitor in a form that simulates routine laboratory preparations and that allows cytogenetic inspection. The system is easy to operate, and it includes a wide range of options for operator interaction to ensure reliability. The results of the computer analysis of the no. 18 chromosomes from five cells from each of 10 different persons demonstrated the usefulness of the system for detecting, measuring, and analyzing individual bands in human populations and its application to establishing band patterns of chromosomes in different states of contraction.

Azure Stains↗