Kristina Friberg

Consistency of chromosomal aberrations in chronic B-lymphocytic leukemia. A longitudinal cytogenetic study of 41 patients

Serial chromosome analyses with a mean of 3.7 samplings during a mean interval of 4.2 years (range, 1.5 to 8.6 years) were performed on B‐cell mitogen‐activated chronic B‐lymphocytic leukemia (CLL) cells from 41 patients. Twenty‐four of these patients (59%) had progressive disease. Clonal chromosomal aberrations were found in 28 patients; 12 had an extra chromosome 12. Thirty patients (73%), 17 with and 13 without clonal aberrations, retained their karyotype throughout the study, although six lost minor subclones. In five patients (12%), a clonal aberration was found only once. Six patients (15%) showed changes of the karyotype. One treated patient with multiple aberrations acquired another monosomy. Another patient with multiple aberrations and prolymphocytic transformation gained a marker chromosome. One treated patient with an initially normal karyotype acquired two independent clonal aberrations. Three patients lost one subclone but retained another clone that increased in frequency. In two cases, clonal changes were associated with clinical changes. The chromosomal aberrations are mostly established already at diagnosis and mark the disease of the CLL patient. Cytogenetic analysis at any time is representative and useful in the prognosis prediction.

Role of chromosomal abnormalities in chronic lymphocytic leukemia.

Chromosomal aberrations occur in both B-CLL and T-CLL. The polyclonal B-cell mitogens, in particular Epstein-Barr virus and lipopolysaccharide from E. coli, have been used successfully to reveal chromosomal abnormalities in 40-60% of patients with B-CLL, while T-cell mitogens have shown chromosomal aberrations in T-CLL. The most common clonal chromosomal aberration in B-CLL is an extra chromosome 12, alone or together with other abnormalities. Other common aberrations are 14q+, structural aberrations on 6, 11, 12 and 13. Proto-oncogenes are frequently located close to breakpoints. The proto-oncogene c-K-ras is located on chromosome 12 and an abnormal transcript has recently been implicated in a subset of B-CLL-patients. An extra chromosome 12 as well as multiple chromosomal abnormalities in B-CLL appear to predict a less favourable prognosis. T-CLL is in most patients characterized by an inv(14), an extra 8q and structural abnormalities in chromosome 7. The genes for the specific T-cell receptor as well as the immunoglobulin heavy chain are located on these chromosomes. Chromosomal aberrations appear to have pathogenetic importance in both B-CLL and T-CLL.

Del(3)(p13) in B-prolymphocytic leukemia—A new nonrandom chromosomal aberration possibly related to the c-ras oncogene☆

Cytogenetic analysis was performed on the leukemic cells from two patients with B-prolymphocytic leukemia. Both patients had del(3)(p13) chromosomal abnormality, as well as other clonal aberrations. Del(3p) was previously reported in one case of B-cell prolymphocytic leukemia, and is known to be a specific aberration in small-cell carcinoma of the lung. In B-cell prolymphocytic leukemia, as in other B-lymphocytic leukemias/lymphomas, the karyotype often involves chromosomes #3, #6, #11, and #12. All of these chromosomes are suggested sites for the c-ras oncogene family.

A new translocation involving three chromosomes in chronic myelocytic leukemia, 46,XY,t(9;11;22)

Bone-marrow metaphases in a 63-year-old male with newly discovered chronic myelocytic leukemia (CML) showed a complex translocation involving chromosomes 9, 11, and 22. About half of the short arm of chromosome 11 was translocated to the terminal part of the long arm of chromosome 9, and the missing fragment on chromosome 22 was translocated to the short arm of the abnormal chromosome 9. The clinical features were typical of CML, and the patient is in good physical condition 10 months after diagnosis on a regimen of busulfan.

Chromosomal Aberrations in Progressive and Indolent Chronic B-Lymphocytic Leukaemia: A longitudinal study

Chromosome analyses of B-cell mitogen-activated cells from 95 patients with chronic B-lymphocytic leukaemia revealed clonal chromosomal aberrations in 50 patients (53%), of which 24 had an extra chromosome 12 with or without other aberrations. Patients with clonal aberrations, especially those with +12, had poorer survival than other patients. Longitudinal studies, with a mean of 3.5 samplings during a median interval of 3.5 years, were performed in 41 patients, of which 24 (59%) had progressive disease. Twenty-nine of the patients in the longitudinal study (71%), 16 with and 13 without clonal aberrations, retained their karyotype unaltered. In 6 patients a clonal aberration was found only once. Six patients showed minor changes of the karyotype. The karyotype seems to be established at diagnosis, and marks the disease of the individual CLL-patient.

Ph chromosome and B-cell malignancy-associated chromosomal aberrations in non-leukaemic immunoblastic B-cell lymphoma

A 62-year-old female with a microK phenotypic immunoblastic B-cell lymphoma with bone marrow involvement but without leukaemia is reported. Bone marrow cells, cytogenetically studied at diagnosis, showed a Philadelphia chromosome due to a (9p;22q) translocation, deleted chromosomes 3 and 6, a 14q+ marker, and two extra chromosomes 18. The Ph chromosome is previously only once reported in a well-characterized B-cell lymphoma, whereas the latter aberrations are common findings in B-cell malignancies.

Translocation between chromosome 7 and chromosome 22, t(7;22)(p22;q12), in a patient with chronic myelocytic leukemia

SummaryA 46-year-old man with chronic myelocytic leukemia had a new variant translocation between chromosome 22 and chromosome 7 in bone marrow cells. No involvement of chromosome 9 was seen. The patient entered blastic transformation within half a year, by which time he had acquired an isochromosome 17 in addition to the variant translocation.

Chromosomal aberrations in leukemic low-grade malignant B-cell lymphoproliferative neoplasias

The low-grade malignant B-cell lymphoproliferative disorders with leukemic cells in the peripheral blood (LMBLL) are practically all included in what is usually called chronic lymphocytic leukemia (CLL). When it became obvious that CLL was a heterogenous disease, it was subdivided in several groups, e.g. according to the Kiel classification [1]. New entities such as immunocytoma, prolymphocytic leukemia, and centrocytic lymphoma, were separated from CLL. Our original aim was to investigate the ‘classical’ CLL for possible presence of specific chromosomal aberrations. The study includes patients within the new subgroups, but only those who presented with a leukemic picture, i.e. a blood lymphocyte count of at least 5 × 109/1.