Interstitial insertion of AF10 into the ALL1 gene in a case of infant acute lymphoblastic leukemia.

The ALL1 gene at 11q23 is a promiscuous gene participating in chromosomal abnormalities of acute leukemias with 1 of over 30 potential partner genes. Among these, the AF10 gene at band 10p12 has been recently cloned and characterized. Acute leukemias with the ALL1/AF10 chimeric gene frequently show heterogeneity in the breakpoints on 10p, as well as complex insertion (10;11) as a result of complex molecular mechanisms leading to the ALL1/AF10 fusion. In this context, we report the first description of an infant acute lymphoblastic leukemia with an interstitial insertion of the AF10 gene into the 11q23 band, resulting in the transcription of the ALL1/AF10 fusion product. Furthermore, we show how different diagnostic tools such as molecular, cytogenetic, and fluorescence in situ hybridization (FISH) analyses should be combined to resolve complex situations in the 11q23 setting.

Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.

Three patients, with constitutional trisomy 8 mosaicism (CT8M), who developed a malignancy are reported. The diagnoses were refractory anaemia, acute lymphoblastic leukaemia, and idiopathic myelofibrosis. In the child with acute leukaemia, the CT8M was diagnosed at birth due to severe dysmorphisms and malformations; the other two patients showed a milder phenotype, and the CT8M was diagnosed only after the finding of trisomy 8 in neoplastic cells. The review of eight similar, previously reported cases and the clinical, cytogenetic, and molecular studies performed in our patients led us to make the following observations: (I) CT8M predisposes to neoplasms, preferentially to myelo- or lymphoproliferative diseases; (2) a gene dosage effect for glutathione reductase in red blood cells was seen in two of our patients; (3) the wide phenotypic variation of CT8M was confirmed: trisomy 8 in neoplastic cells of phenotypically near-normal cases may be misinterpreted as acquired; and (4) molecular studies suggested a postzygotic origin of the trisomy in our three cases, with the supernumerary chromosome being of paternal origin in one case and of maternal origin in the other two. We postulate that the trisomy 8 in neoplasms may often occur by mitotic nondisjunction in an early embryonic multipotent cell and that what is usually interpreted as an acquired trisomy 8 may in fact be CT8M. The constitutional trisomy 8 would act as a pathogenetically important first mutation in multistep carcinogenesis. Whenever trisomy 8 is found in malignancies, the patient should be reevaluated clinically to exclude CT8M, and CT8M patients should be monitored for the possible development of malignancies.

Characterization of a new case of trisomy 8 in acute lymphoblastic leukemia.

Trisomy 8 is a relatively common finding in acute nonlymphoblastic leukemia (ANLL). In childhood acute lymphoblastic leukemia (ALL) it apparently is much more rare. Although Human Gene Mapping 11 included trisomy 8 as a marker for a subgroup of ALL, morphologic and immunologic characteristics of this entity have not been defined. We describe a case of early T-cell ALL (T-ALL) in a pediatric patient in whom this abnormality was the sole chromosome aberration. In situ hybridization with a chromosome 8-specific alpha-satellite DNA probe was performed. Our data are discussed and compared with pertinent literature.

Peripheral blood stem cells in children with solid tumors. Part I. Feasibility and application.

A method for collecting peripheral blood mononuclear cells following mobilizing chemotherapy in pediatric patients is described. The critical elements of the method included temporary heparinization of the patient to reduce citrate overload, and limiting extracorporeal circulation to 15% of the patient's blood volume using packed red blood cells and albumin. A median of 0.9 x 10(8) mononuclear cells/kg per collection were harvested in 40 collections from eight patients with only one episode of fever and chills. Peripheral blood stem cells were reinfused into six of these patients with refractory/recurrent pediatric tumors after intensive chemotherapy. Bone marrow reconstitution followed with a mean of 30 days (19-38) for absolute neutrophils and 48 days (32-275+) for platelets. Previous chemotherapy did not appear to affect peripheral blood stem cell efficacy in reconstituting chemotherapy-ablated bone marrow.

Unusual t(3;12)(q28;q13) in childhood acute lymphoblastic leukemia.

In this article we report a case of a 7-year-old boy affected by acute lymphoblastic leukemia of the common type. Bone marrow examination at diagnosis showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12. This previously unpublished translocation is discussed and compared to the findings in the current literature.

An improved technique for peripheral blood stem cell collection in small patients.

Peripheral Blood Stem Cell collection in adults is a consolidated method for autografting. The same procedure is less easily performed in pediatric patients due to low weight, vascular access problems and anticoagulant side effects. Great efforts have been made to overcome technical difficulties and make apheresis in children a reliable and safe procedure.