Background: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three-to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease.Methods: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immunophenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted.Results: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 ؋ 10

1 Purine analogues have been examined for anxiolytic-and anxiogenic-like activity in mice, by use of the elevated plus-maze.2 The selective Al receptor agonist, N6-cyclopentyladenosine (CPA) had marked anxiolytic-like activity at 1O and 50 gg kg-, with no effect on locomotor performance at these doses.3 The Al selective adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (CPX) had no significant effect on anxiety-related measures or locomotor behaviour, but blocked the anxiolytic-like activity of CPA. The hydrophilic xanthine, 8-(p-sulphophenyl) theophylline did not prevent anxiolysis by CPA. 4 Caffeine had anxiogenic-like activity at 30 mg kg-' which was prevented by CPA at 50 Yg kg-. 5The A2 receptor agonist, Nl-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) had no effect on anxiety behaviour but depressed locomotor activity at the highest dose tested of 1 mg kg-'. The A2 receptor antagonist, 1,3-dimethyl-1-propargylxanthine (DMPX) had no effect on anxiety-related measures or locomotion and did not modify the anxiolytic-like activity of CPA. 6 Administration of DPMA in combination with anxiolytic doses of CPA prevented the anxiolytic-like activity of the latter.7 The results suggest that the selective activation of central Al adenosine receptors induces anxiolyticlike behaviour, while the activation of A2 sites causes locomotor depression and reduces the effects of Al receptor activation. The absence of any effect of CPX alone suggests that the receptors involved in modulating behaviour in the elevated plus-maze in mice are not activated tonically by endogenous adenosine.

Our results demonstrated the contributory role of neuroactive steroid 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol. It is speculated that ethanol-induced modulation of endogenous GABAergic neurosteroids, especially 3alpha, 5alpha-THP, might be crucial pertinent to the etiology of 'trait' anxiety (tension reduction) and ethanol abuse.

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In an ongoing study, families with two or more living cases of B-CLL in first-degree relatives have been recruited through physician and self-referral. Since 1967, 28 kindreds with 73 cases of B-CLL have been enrolled within the National Cancer Institute (NCI) Familial B-CLL Registry. Medical, clinical, and demographic information have been obtained from private physicians, patient interview, hospital records, and death certificates. We used SEER Registry data to compare characteristics of sporadic B-CLL to familial B-CLL. The mean age at diagnosis was approximately 10 years younger among familial cases (57.9 +/- 12.1) than that observed in sporadic cases (70.1 +/- 11.9). A higher percentage of second primary tumors among familial CLL cases compared to reports in sporadic was also observed (16% vs. 8.8%). However, the transformation rate to non-Hodgkin's lymphoma does not appear to be different from that reported for sporadic cases. In conclusion, we observed some differences between familial and sporadic cases; whether any of these characteristics affect survival time or severity of disease is unknown. The study of families with multiple B-CLL cases will aid in delineating the genes and environmental factors that may play a role in the development of both forms of B-CLL.