Correspondence 1907 spermatogenesis continues from puberty up to old age, there is more Alaez, Miriam Va´zquez and Gabriela de la Rosa for their very opportunity for preconceptional mutant gene accumulation in men helpful discussions. We also thank Mtra Sylvia Garcı´a of the John than in women. Benzo[a]pyrene is a potent carcinogen in cigarette Langdon Down Institute and to Dra Susana Ramı´rez Robles, Lic Ma smoke, its reactive metabolite induces DNA adducts, which can de los Angeles Rojas Ramı´rez and Dr Pedro Gonza´lez Vivanco of cause mutations. These DNA adducts were found in spermatozoa of the Integral Care for Persons with Down’s Syndrome (CTDUCA) for a smoker and his embryo.6 The 8-hydroxy-20- deoxyguanosine (8- providing the DS children included in this study. OhdG), a biomarker for oxidative DNA damage associated with 1,2 1 decreases in indices of sperm quality such as sperm number and JM Mejı´a-Arangure´ The Medical Research Unit on Clinical A Fajardo-Gutie´rrez1 Epidemiology, Hosp. de Pediatrı´a, sperm motility, was also found to be increased in these cases, 1,2 damaging the offspring. The early age peak in ALL (2–5 years) and H Flores-Aguilar Centro Me´dico Nacional Siglo XXI, IMSS, MC Martı´nez-Garcı´a1 Mexico; below 1 year in AML, support the hypothesis of environmental 3 2The Deptartment of Immunogenetics, exposure during gestation and preconception as being involved in F Salamanca-Go´mez V Palma-Padilla3 Instituto de Diagno´stico y Referencia its development. It is unknown as to which events might precipitate 4 Epidemiolo´gicos, SS, Mexico; R Paredes-Aguilera 3 the chromosome breaks whose improper repair initiates or promotes R Berna´ldez-Rı´os5 The Unit of Medical Research on Genetics, childhood AL. For paternal alcohol consumption, the mechanisms A Ortiz-Ferna´ndez6 Hosp. de Pediatrı´a, Centro Me´dico Nacional related with AL development, in their offspring, are similar to those 7 Siglo XXI, IMSS, Mexico; A Martı´nez-Avalos 4 described for smoking.7 2 The Department of Haematology, C Gorodezky Inst. Nacional de Pediatrı´a, SS, Mexico; Passive child exposure to tobacco smoke had a higher risk than the 5 one reported elsewhere. As shown by others,8 when several subjects The Department of Haematology, Hospital de Pediatrı´a, Centro Me´dico Nacional Siglo XXI, smoked in front of the child, the risk was evident; large amounts of IMSS, Mexico; carcinogenic, volatile nitrosamines and aromatic amines are present 6The Department of Haematology, Hospital in the inhaled smoke stream, although the concentration of these General, Centro Me´dico Nacional La Raza, compounds is about two orders of magnitude lower than IMSS, Mexico; in active cigarette smokers, suggesting that some risk genotypes 7The Department of Oncology, Hospital Infantil are particularly susceptible to low doses of carcinogens. It has de Me´xico Federico Go´mez, SS, Mexico been claimed that smoke exposure is prevalent among Hispanics and Afro-Americans. In these groups, the population of children is larger than in Caucasians and they are more vulnerable to the toxic effects of environmental tobacco smoke.8 Other possible mechanisms may References include stimulation of angiogenesis and tumor growth promotion by nicotine. Angiogenesis has indeed been associated with AL. 1 Robison LL. Down Syndrome and leukemia. Leukemia 1992; 6: In conclusion, childhood leukemia is a heterogeneous disease with 5–7. individual subtypes in which the response to chemotherapy and its 2 Peto J. Cancer Epidemiology in the last century and the next decade. causes may be different. It is possible that acute leukemia share Nature 2001; 411: 390–395. 3 Siegel M. Smoking and leukaemia: evaluation of causal hypothesis. Am etiologies, as shown for lymphoma or thyroid cancer in children. The J Epidemiol 1993; 138: 1–9. results of this study are encouraging, but the sample size should be 4 Greaves M. Childhood leukaemia. Br Med J 2002; 324: 283–287. increased and other studies in different populations should be 5 Sorahan T, McKinney PA, Mann JR, Lancashire RJ, Stiller CA, Birch JM performed to confirm these data. Research of the risk factors leading et al. Childhood cancer and parental use of tobacco: findings from the to leukemia is relevant to identify strategies to develop protective inter-regional epidemiological study of childhood cancer (IRESCC). Br J policies and interventions. Cancer 2001; 84: 141–146. 6 Zenzes MT, Puy LA, Bielecki R, Reed TE. Detection of benzo[a]pyrene diol eposide-DNA adducts in embryos from smoking couples: evidence for transmission by spermatozoa. Mol Hum Reprod 1999; Acknowledgements 5: 125–131. 7 Infante-Rivard C, Krajinovic M, Labuda D, Sinnett D. Childhood acute This study was supported by Grant G30670-M of the Consejo lymphoblastic leukemia associated with parental alcohol consumption Nacional de Ciencia y Tecnologı´a (CONACyT) and FP-00038/218/ and polymorphisms of carcinogen-metabolizing genes. Epidemiology 415/458/459 of the Instituto Mexicano del Seguro Social. We are 2002; 13: 277–281. 8 Perera FP, Illman SM, Kinney PL, Whyatt RM, Kelvin EA, Shepard P also indebted to the Instituto de Diagno´stico y Referencia et al. The challenge of preventing environmentally related disease in Epidemiolo´gicos who partly supported the study. We are very young children: community-based research in New York City. Environ grateful to Dod Stewart for revising the manuscript; to Carmen Health Perspect 2002; 110: 197–204. Molecular identification of CBFb-MYH11 fusion transcripts in an AML M4Eo patient in the absence of inv16 or other abnormality by cytogenetic and FISH analyses – a rare occurrence Leukemia (2003) 17, 1907–1910. doi:10.1038/sj.leu.2403056 16 abnormalities, which are closely associated with the FAB subtype M4Eo, result in the creation of a fusion gene between the smooth muscle myosin-heavy chain gene (MYH11) at 16p13 and The prognostic and therapeutic significance of karyotype at the core binding factor b (CBFb) gene at 16q22. The fusion protein diagnosis in patients with AML is now fully established. Two of product, CBFb-MYH11, interacts with nuclear corepressors, leading the most common recurring cytogenetic abnormalities in AML are to dysregulation of transcription. Patients with ‘CBF leukemias’ t(8;21)(q22;q22) and the pericentric inversion of chromosome 16, including those with inv(16)/t(16;16) account for up to 20% of inv(16)(p13;q22), or its variant t(16;16)(p13;q22). The chromosome young adult cases of de novo AML. Such patients have a more Leukemia Correspondence 1908 favorable prognosis, particularly when treated with intensive postremission therapy including high-dose cytarabine. Therefore, accurate identification of these patients at diagnosis is of therapeutic significance. a Several recent reports have examined the utility of cytogenetics, FISH, and molecular analyses to detect CBFb–MYH11 fusion transcripts in patients with AML.1–7 In initial reports, patients expressing the CBFb–MYH11 chimeric gene in the absence of b chromosome 16 aberrations were reported to account for up to 43% of all molecularly positive patients.2–4 Other studies have reported a much lower incidence of such discordance between cytogenetic c and molecular analyses.1,5–7 These discrepancies may be a consequence of the difficulty in detecting the inv(16) cytogeneti- cally.8 In all these reports, the expression of CBFb–MYH11 fusion transcripts in the presence of a normal karyotype without chromo- some 16 abnormalities and other cytogenetic aberrations was rare. In the studies providing information on the number of patients with a normal karyotype, the incidence of molecularly positive disease was 1.5% (one of 65),2 1.1% (one of 87),7 and 0.8% (one of 124)1. In the latter study, the single patient initially reported as having a normal karyotype was found to have inv(16) on re-examination.1 In the study of 412 patients by Rowe et al.,5 no instances of a positive PCR result without a cytogenetically detectable chromosome 16 aberration were reported. Ritter et al 4 reported three such patients with normal cytogenetics and the presence of the fusion gene by molecular analysis. Our patient, a 23-year-old African-American male, presented in December of 2001 with a 1-month history of fatigue, progressive shortness of breath and abdominal pain. At the time of diagnosis, he had an elevated white blood cell (WBC) count of 265  109/l with 30% leukemic blasts, hemoglobin of 8.3 g/dl, and a platelet  9 count of 109 10 /l. Other significant abnormal laboratory findings Figure 1 Normal chromosomes 16 as demonstrated by cytoge- included a serum LDH of 1641 m/l and a pO2 of 62 mmHg. On netic and fluorescence in situ hybridization analyses. (a) Ideogram of examination he was dyspneic and tachypneic but afebrile, with chromosome 16 and two pairs of chromosomes 16 from the initial stable hemodynamic indices. He also had clinically evident diagnostic specimen. (b) Ideogram and three pairs of chromosomes 16 bilateral pleural effusions and generalized abdominal discomfort from the most recent study at relapse. The two pairs on the right are with no rebound tenderness or rigidity. Bone marrow examination from cells that also contained the deleted chromosome 7. (c) showed extensive replacement with leukemic cells, which were Hybridization of the Vysis CBFb probe to a metaphase and an positive for surface markers CD13, CD33, HLA-DR, CD14, CD15, interphase cell from the most recent study. This probe, break apart in CD11C, CD11b, and MPO, supporting the diagnosis of AML M4. design, is the one most commonly used for clinical detection of the inverted chromosome 16. Normal cells, such as the ones shown here, A relative increase in eosinophilic precursors was also noted.