Anticipation in familial leukemia.

Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22.     

Use of monoclonal antibodies as a diagnostic tool in human leukemia. I. Acute myeloid leukemia and acute phase of chronic myeloid leukemia

Various monoclonal antibodies (mAbs) detecting certain different epitopes on myeloid cells (VIMD5, D5 D6, OKM1, Leu-M3, VIEG4, OKIa 1) have been used in combination with conventional markers (antihuman myeloid hetero-antiserum, FcIgG-receptors, C3d-receptors) to further define the phenotypic heterogeneity of myeloid leukemia. Subsequent leukemic samples from previously untreated patients with acute myeloid leukemia (AML) (51 adults, 24 children) and from nine adult patients in the acute phase of chronic myeloid leukemia (CML-BC) were studied. It was possible to demonstrate quantitative differences in the expression of antigens on the various leukemia subtypes which could be exploited for diagnosis. Furthermore our results revealed that there is a very close correlation between the different surface phenotypes and the types morphologically assessed according to FAB-criteria.     

Acute eosinophilic leukemia. An ultrastructural study.

Observations on a 32 year old male are described. Hematological examination demonstrated leukocytosis with circulating blastosis and dystrophic hypereosinophilia of the blood and bone marrow, with cells at various stages of maturation. Cytotoxic chemotherapy led to complete remission for 5 months followed by a terminal relapse. No features in favor of an "eosinophilic collagenosis" were revealed at autopsy. Repetitive ultrastructural studies performed during evolution of the illness demonstrated considerable anomalies of the eosinophil line. The present observation thus shows the clinical, evolutional, cytological and autopsy criteria of an acute eosinophilic leukemia.     

Oncogenicity of AKR endogenous leukemia viruses.

Four biologically distinct groups of endogenous murine leukemia virus (MuLV) have been isolated from AKR mice. These viruses included (i) ecotopic XC+ MuLV that occur in high titer in normal tissues and serum of AKR mice throughout their life span, (ii) ecotropic XC- MuLV that are produced in high titers by leukemia cells, (iii) xenotropic MuLV that are readily demonstrable only in aged mice, and (iv) polytropic MuLV thatarise in the thymuses of aged mice as a consequence of genetic recombination between ecotropic and xenotropic MuLV. Virus of each of these biological classes were assayed in AKR mice for their ability to accelerate the occurrence of spontaneous leukemia. Certain isolates of ecotropic XC- MuLV and polytropic MuLV were found to have high oncogenic activity. These viruses induced 100% leukemias within 90 days of inoculation. In contrast, ecotropic XC+ MuLV that were obtained from AKR embryo fibroblasts and xenotropic MuLV that were obtained from the lymphoid tissues of aged AKR mice did not demonstrate oncogenic activity. These findings demonstrate fundamental differences between XC- and XC+ ecotropic MuLV that are found in leukemic and normal tissues, respectively. Furthermore, these findings point to the role of ecotropic XC- and polytropic MuLV in the spontaneous leukemogenesis of AKR mice.