 Leukemia & Lymphoma, March 2015; 56(3): 826–828 © 2014 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2014.939968 Correspondence: Francesco Albano, MD, Department of Emergency and Organ Transplantation (DETO), Hematology Section, University of Bari, P.zza G. Cesare, 11, 70124 Bari, Italy. Tel: + 39(0)80-5478031. Fax: + 39(0)80-5508369. E-mail: francesco.albano@uniba.it Received 14 May 2014; revised 19 June 2014; accepted 23 June 2014 LETTER TO THE EDITOR Centromeric fragment of chromosome 7 in atypical chronic myeloid leukemia with the SET binding protein 1 gene mutation Nicoletta Coccaro, Giuseppina Tota, Luisa Anelli, Antonella Zagaria, Paola Casieri, Angelo Cellamare, Angela Minervini, Crescenzio Francesco Minervini, Claudia Brunetti, Alessandra Ricco, Paola Orsini, Cosimo Cumbo, Giorgina Specchia & Francesco Albano Hematology Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy Atypical chronic myeloid leukemia (aCML) is a rare hema- tological malignancy with a relative incidence estimated at 1–2 cases per 100 patients with BCR–ABL1-positive CML. Te 2008 World Health Organization (WHO) classifcation identifed aCML as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) and specifed some diagnostic cri- teria [1], such as neutrophilic leukocytosis with a left shift associated with marked granulocytic dysplasia. Recently, SET binding protein 1 ( SETBP1) gene mutations have been detected in 25–32% of patients with aCML [2,3]. Moreover, the colony stimulating factor 3 receptor ( CSF3R) gene muta- tion has been reported alone or in association with SETBP1 gene mutation [4]. At present, the frequency of CSF3R gene mutations in aCML is still controversial, being reported as similar to the frequency in chronic neutrophilic leukemia (CNL) or else essentially absent [4,5]. SETBP1 mutations identifed in aCML were located in a short stretch of 14 resi- dues spanning Glu858 to Ile871 within the SKI domain. Te most frequently observed alterations were p.Asp868Asn and p.Gly870Ser [2,3]. Moreover, an association between SETBP1 gene mutations and the presence of monosomy 7 or isochromosome i(17)(q10) has been reported [2]. We describe a case of aCML characterized by the SETBP1 mutation and the presence of centromeric residues of chromosome 7 detected by molecular cytogenetic analysis, whereas karyotypic analysis showed monosomy 7. A 63-year-old man was admitted to our department with leukocytosis, anemia and thrombocytopenia (hemo- globin 11.4 g/dL, total leukocytes 29  10 9 /L, platelets 74  10 9 /L). A peripheral blood flm showed neutrophilia (90% neutrophils), consisting of 70% mature neutrophils and 20% precursors, both associated with dysplasia. Physi- cal examination showed mild hepatosplenomegaly. Te bone marrow was hypercellular with proliferation and dysplasia of the granulocytic lineage. Megakaryocytic dys- plasia was also observed [Figure 1(A)]. Molecular analysis did not show evidence of the BCR–ABL1 rearrangement or JAK2 V617F mutation. Moreover, fuorescence in situ hybridization (FISH) experiments showed no involvement of the PDGFRB, PDGFRA and FGFR1 genes in any kind of chromosome translocation or deletion. Terefore, accord- ing to the 2008 WHO criteria a diagnosis of aCML was made. Te patient was started on hydroxyurea treatment. Tree months after the end of treatment the white blood cell (WBC) count was fairly well controlled. Karyotyping was performed at diagnosis on bone marrow cells according to standard methods [6]. Karyotypic analysis revealed 45,XY, - 7[20] [Figure 1(B)]. FISH experiments were carried out to confirm mono- somy of chromosome 7 detected by conventional cytoge- netics. FISH analyses were performed on bone marrow (BM) samples at the onset of aCML, using bacterial artifi- cial chromosomes (BACs) and an alphoid probe according to the University of California Santa Cruz (UCSC; http:// genome.ucsc.edu/; February 2009 release) database. Chromosome preparations were hybridized in situ with probes labeled by nick translation [7]. For chromosome 7 analysis pZ7.5, a home-brew probe specific for alphoid DNA, and the BACs RP11-795E2 (chr 7: 57 761 054–57 950 959) and RP11-1025O20 (chr 7: 61 092 810–61 266 803), mapping near the pericentromeric region, were employed in a co-hybridization experiment. BACs were validated on normal metaphases obtained from healthy donor peripheral blood T lymphocytes to rule out non-specific binding. FISH analyses confrmed the occurrence of chromosome 7 monosomy; however, the presence of a small centromere portion consisting solely of alphoid DNA was revealed in most of the analyzed cells (about 75%). In fact, on this small fragment, a fuorescent signal was generated only by probe pZ7.5, specifc for alphoid sequences of chromosome 7 [Figure 1(C)]. To investigate the size of this small chromo- some fragment, we used BAC clone RP11-795E2 immedi- ately upstream of the centromere on 7p, and BAC clone RP11-1025O20 immediately downstream of the centromere on 7q; neither showed any fuorescent signal [Figure 1(C)].