Pediatric Hematology and Oncology, 25:582–597, 2008 Copyright C  Informa Healthcare USA, Inc. ISSN: 0888-0018 print / 1521-0669 online DOI: 10.1080/08880010802237450 RUNX1 ABERRATIONS IN ETV6/RUNX1-POSITIVE AND ETV6/RUNX1-NEGATIVE PATIENTS: Its Hemato-Pathological and Prognostic Significance in a Large Cohort (619 Cases) of ALL Anurita Peter Pais, MSc, PhD, Pratibha S. Amare Kadam, MSc, PhD, and Gauri Chandrakant Raje, MSc ✷ Tata Memorial Hospital, Cancer Cytogenetics Laboratory, Parel, Mumbai, India Shripad Banavali, MD, Purvish Parikh, MD, Purna Kurkure, MD, and Brijesh Arora, MD ✷ Tata Memorial Hospital, Department of Medical Oncology, Parel, Mumbai, India Sumit Gujral, MD, S. Ashok Kumar, and Y. Badrinath ✷ Department of Pathology, Parel, Mumbai, India ✷ A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell precussor ALL, indicating no geographical heterogeinity. Association of CD34-negative phenotype, peak incidence in the 3- to 7-year age group, and a comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1- positive cases were distinct findings in this series. Additional genetic changes, such as ETV6 loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1- positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model that these secondary changes are necessary for leukemogenesis rather than progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1-negative group of BCP-ALL that encourages the investigation of RUNX1 at a large scale with longer follow-up, which will focus on the prognostic importance and the underlying biology of disease. Keywords additional isolated aberrations, BCP-ALL, FISH, ETV6/RUNX1 Received 10 October 2007; accepted 2 May 2008. We acknowledge Lady Tata Memorial Trust (LTMT), Mumbai, for providing the financial support for the present study. Address correspondence to Pratibha S. Amare Kadam, PhD, Cancer Cytogenetics Labora- tory, 7th Floor, Annex Bldg, Dr. Ernest Borges Marg, Parel, Mumbai 400012, India. E-mail: prati- bha.amare@gmail.com 582