Kong-Oo Goh

Evidence of clastogens in acute leukemia. Chromosomal abnormalities in healthy parents of congenital leukemic patients.

If leukemia is caused by an “agent” which can pass through the placenta, it could produce leukemic transformation in the maternal cells. Cytogenetic studies were carried out in 5 acute lymphoblastic leukemic children and their parents. Significant abnormalities were found in 3 of the fathers, 4 of the mothers, and all the leukemic children. All but one abnormal metaphase from the mothers of the 2 leukemic boys had a XX sex pattern, indicating that these abnormal metaphases originated in the mother and probably were caused by a chromosomal breaking agent. The abnormal metaphases found in the fathers suggests that they too were exposed to this agent. Therefore, this agent must be present in the immediate environment, and this can pass from the maternal circulation to the fetus through the placenta and affect the fetus cells. The failure of the infant to eradicate these abnormal cells results in the phenotypical expression of clinical leukemia. Cancer 46:109–117, 1980.

Myeloproliferative disorder in a t(13q14q) carrier.

A Robertsonian balanced translocation of two D chromosomes was found in the bone marrow cytogenetic studies of a 70‐year‐old myeloproliferative disorder (MPD) woman. G‐banding studies showed the translocation involved a 13q14q. An identical balanced t(13q14q) chromosomal pattern was found in her peripheral blood 3 years before the diagnosis of MPD as part of an investigation involving her daughters reproductive difficulties. Her daughter is also a t(13q14q) balanced translocation carrier. The finding of a t(13q14q) in MPD may be coincidental or it may be predisposing to the development of MPD. Additional studies may elucidate this controversy.

Chromosomes and B and T cells in mycosis fungoides.

Because mycosis fungoides (MF) and Sézary syndrome (SS) share several features, some investigators have considered them to be different stages of the same disease. Others view them as separate entities. Cytogenetic studies in four typical MF patients showed that the chromosomal abnormalities were different from those reported in SS patients, and the abnormalities were found with almost equal frequency in both B and T cells. In addition, we found the frequencies of the T cells in six of the eight peripheral blood determinations in three patients were within normal range. These observations support the possibility that MF and SS are two separate disease entities.

Abnormal chromosome in Prader-Willi syndrome.

A Prader‐Willi Syndrome (PWS) patient was found to have an extra satellite chromosome, smaller than the normal Chromosome 22, in 60% of her metaphases. G‐ and C‐bandings showed that the extra chromosome did not derive from a Chromosome 15 as has been reported in some PWS patients. Because of variation in chromosomal abnormalities in the PWS patients reported, it was concluded that the chromosomal abnormalities found in them may be a secondary phenomenon rather than the cause of PWS.

Chromosomal abnormalities in chronic lymphocytic leukemia.

Peripheral blood lymphocytes from five chronic lymphocytic leukemia (CLL) patients were cultured with PHA for 3-6 days. Chromosomal analysis with G-banding showed 25% of the diploid metaphases were pseudodiploid as a result of either a chromosomal deletion or a translocation. Abnormal clones with 18p- were seen in two patients, and two other patients had 18p- metaphases, but with other inconsistent abnormal chromosomes. None of the patients had trisomy 12, which has been thought by some to carry a poor prognosis. Although no conclusion can be reached regarding the significance of the chromosomal abnormalities in CLL, the type of chromosomal abnormalities in these patients suggests that they are the result of chromosomal breakage and abnormal repair.

Leukemia in radiation-treated patients: cytogenetic studies in eight cases

Abnormal chromosomes have been found in various clinical settings and in cancer patients. Eight patients developed leukemia several years after the diagnosis and treatment of a primary malignant disease. All the patients were being treated with irradiation, and five of them also received chemotherapy, notably, alkylating agents. The type of leukemias and the interval between irradiation and leukemia parallel very well with those reported from the atomic bomb casualties. Chromosomal abnormalities were seen in all the patients. These abnormalities have been reported in irradiated normal persons without developed leukemias. These findings suggest that the development of clinical cancer or leukemia may depend, not only on the presence of abnormal cells, but also on other factors. Perhaps the environment that allowed the original cancer to develop in our patients is capable of allowing the radiation-induced abnormal cells to be expressed as clinical leukemia.

Additional Philadelphia chromosomes in acute blastic crisis of chronic myelocytic leukemia: possible mechanism of producing additional chromosomal abnormalities.

Detailed chromosomal analyses of eight patients with an acute blastic crisis (ABC) of chronic myelocytic leukemia (CML) who had two (diplo) or three (triplo) Philadelphia (Ph1) chromosomes showed all patients have marked aneuploidy. Seven were hyperdiploid and one hypodiploid. The mechanism involved in the chromosomal abnormalities, other than the Ph1 chromosome was thought due to nondisjunction in mitosis. The most simple explanation for the nondisjunction would be that it occurs more frequently in cells which are already chromosomally imbalanced.

Induction of micronuclei in PHA-stimulated human lymphocyte cultures by therapeutic radiation

Micronuclei frequency and percent of chromosome breaks increases significantly in adults whose thymus glands were irradiated in infancy and after irradiation of cancer patients.

Chromosomal aberrations in lymphocytes of normal adults long after thymus irradiation

GOH, K. 0., REDDY, M. M., AND HEMPELMANN, L. H. Chromosomal Aberrations in Lymphocytes of Normal Adults Long after Thymus Irradiation. Radiat. Res. 67, 82-85 (1976). Cytogenetic studies from the cultured peripheral blood lymphocytes were carried out on 12 normal adults who were treated with X radiation for thymus enlargement during early childhood and five normal controls. The frequencies of the abnormal cells and chromosomal breakages were higher in the thymus-irradiated subjects than in the controls.

Abnormal chromosomes in histocytic lymphoma

Five of six diffuse histocytic lymphoma patients had chromosomal abnormalities. Four had abnormal clones; three, a large acrocentric chromosome (LAC); and one, an abnormal large submetacentric chromosome (LSC). The LAC was a 14q+ and the LSC, a 4q+. Although no cytogenetic abnormality was found in a normal lymph node of a patient whose diseased lymph node had an LAC, abnormal chromosomes were seen in three patients with normal morphological bone marrow and in two peripheral blood specimens with a normal differential count. Since staging is important in aiding the clinician to select the type of treatment in this disease, it is recommended that cytogenetic studies in all biopsied tissues should be done as part of an overall diagnostic procedure in patients suspected of this disease.