Two distinct leukemia syndromes are associated with abnormalities of chromosome band 8p11. First, a myeloproliferative disorder with features characteristic of both chronic myeloid leukemia and non-Hodgkin's lymphoma and second, an acute myeloid leukemia (AML) with French-American-British (FAB) M4/5 morphology and prominent erythrophagocytosis. The two syndromes are exemplified by a t(8; 13)(p11; q12) and a t(8; 16)(p11; p13), respectively, but cytogenetic variants of both have been described. Recently, the t(8; 16) has been cloned and shown to fuse the MOZ gene at 8p11 to the CBP gene at 16p13. We have used fluorescence in situ hybridization (FISH), Southern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) to refine the 8p11 breakpoint in three cases with t(8; 13)(p11; q12) and in a single case of AML-M5 with a clinical picture apparently identical to that found in patients with a t(8; 16), but characterized by an inv(8)(p11q13). FISH analysis was performed with several 8p11 CEPH yeast artificial chromosome (YAC) clones. YAC 782H11 was centromeric to the one case with t(8; 13) tested, but was telomeric to the inv(8). YAC 847B12 was telomeric to both the t(8; 13) and the inv(8), whereas YAC 829D12 was centromeric to the t(8; 13), but split by the inv(8). Southern blotting and PCR of YAC 829D12 showed that it contained the MOZ gene. A 900-bp MOZ fragment encompassing the published t(8; 16) breakpoint was amplified by PCR from normal peripheral blood leukocyte cDNA and used to probe Southern blots of patient DNA. A rearrangement was detected in the case with inv(8), but not in any of the three cases with t(8; 13). Southern blotting with a CBP probe and RT-PCR with MOZ and CBP primers suggested that the inv(8) does not result in a cryptic MOZ-CBP fusion. It is likely, therefore, that MOZ is fused to a novel gene at 8q13 in this case. We conclude that the t(8; 13) breakpoint is flanked by YACs 782H11 and 847B12 and is at least 1 Mb telomeric to MOZ. MOZ is involved, however, in a new variant of the t(8; 16).

Summary.We describe two patients with acute myeloid leukaemia (AML) associated with erythrophagocytosis and a pericentric inversion of chromosome 8, inv(8)(p11q13). The haematological features were indistinguishable from those of patients with the t(8;16) syndrome and its variants. Our observations emphasize the importance of the breakpoint at 8p11 and the possible involvement of the MOZ gene in all these cases.Keywords: acute myeloid leukaemia, M4/M5 subtypes, erythrophagocytosis, t(8;16), cytogenetic variant.The translocation t(8;16)(p11;p13) is a rare cytogenetic abnormality which almost always accompanies a diagnosis of acute myelomonocytic leukaemia (AML FAB-M4) or acute monocytic leukaemia (AML FAB-M5) with erythrophagocytosis by the leukaemic blasts. Several variants, always with the 8p11 breakpoint, have been reported, most notably t(8;19) and t(8;22) (Lai et al, 1992;Stark et al, 1995). A further variant is presented here, seen in two patients with the clinical features of this rare AML subtype. CASE REPORTS Patient 1A 15-year-old Indian girl was referred from another hospital for further investigation and treatment of acute myeloid leukaemia. On examination she was not distressed. There were no ecchymoses, petechiae, peripheral lymphadenopathy or abdominal organomegaly. She was febrile, 38ЊC, with no evidence of any infective focus. Mild gum hyperplasia was present and there was an acneiform rash on the face and back. Investigation revealed a haemoglobin of 9·8 g/dl (posttransfusion), white cell count of 1·0 × 10 9 /l with a neutrophil count of 0·1 × 10 9 /l and platelets 99 × 10 9 /l. Occasional large blasts were present on the blood film. The prothrombin time was prolonged at 17·8 s (normal 13-15 s); this was later shown to be due to a mild factor VII deficiency. The APTT, thrombin time and fibrinogen were normal. The bone marrow aspirate was hypercellular with 98% blasts. These were large with basophilic cytoplasm, scanty granulation and a low nuclear/cytoplasmic ratio. No Auer rods were seen. Phagocytosis of erythroid and granulocyte precursors was prominent, with many blasts showing single or multiple clear phagosomes (Figs 1a and 1b). Mitotic figures were prominent. The majority of blasts were weakly positive with alpha-naphthyl butyrate esterase (monocytic) and < 5% positive for chloroacetate esterase (granulocytic). The morphological features and immunophenotyping were consistent with a diagnosis of AML, FAB-M5a.Cytogenetic analysis was performed on 10 metaphases from unfractionated bone marrow, cultured using standard methods. Seven showed a pericentric inversion of one chromosome 8, with breakpoints at p11 and q13 (Fig 2a) and the remaining three metaphases had an apparently normal karyotype. Fluorescence in situ hybridization using a whole chromosome paint for 8 was performed to exclude the presence of a cryptic rearrangement involving any of the usual partner chromosomes in the t(8;V). There was no signal visible on any chromosome other than the normal and inverted chromosome 8s.The patient...

Summary. Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy and mucosal leucoplakia. Bone marrow failure occurs in the majority of cases and there is a predisposition to malignancy. Following conflicting reports of increased spontaneous and induced chromosomal breakage in DC lymphocytes, we examined chromosomal breakage with and without clastogen treatment in 10 DC patients from six different families. Peripheral blood cultures were stimulated with phytohaemagglutinin and treated with three clastogenic agents and g-irradiation. There was no significant difference in the chromosomal breakage in DC lymphocytes with or without exposure to bleomycin, DEB, MMC or g-irradiation. DC can therefore be distinguished from Fanconi's anaemia in which lymphocytes show increased spontaneous and clastogen-induced chromosomal breakage.