t(10;12)(q24;q15): A new cytogenetic marker in hematological malignancies


      • t(10;12)(q24;q15) is a new recurrent cytogenetic abnormality in oncohematology.
      • t(10;12)(q24;q15) is associated with poor outcome in hematological malignancies.
      • t(10;12)(q24;q15) is a new rexurrent cytogenetic abnormality in oncohematology.
      • t(10;12)(q24;q1%) is associated with poor outcome in hematological malignancies.


      Cytogenetic studies have played a crucial role in the discovery of genes involved in several diseases. In the field of oncohematology, cytogenetics is still necessary for the classification and prognosis of many diseases. Here we report a new recurrent chromosome translocation, t(10;12)(q24;q15), in two patients with different hematological malignancies: myelodysplastic syndrome with excess blasts (MDS-EB), and myelofibrosis (MF) secondary to essential thrombocythemia (ET). The chromosome alteration was observed as a sole karyotype change in the patient with MDS-EB, both at the initial diagnosis and following progression to MDS-EB2. A putative HMGA2-KLLN rearrangement by RNA-sequencing was detected in this patient. The patient with ET, had a normal karyotype at diagnosis and the t(10;12)(q24;q15) translocation emerged as a sole cytogenetic alteration after transformation, and when MF was evident. We reviewed the literature to determine whether this chromosome abnormality had previously been described in other hematological patients and found two cases: an aggressive T-cell lymphoblastic lymphoma (T-LBL) and a case of transformed chronic myeloproliferative syndrome (CMS), in both of which t(10;12)(q24;q15) was also the only karyotype change. The clinical evolution of all four cases suggested that t(10;12)(q24;q15) is associated with a poor outcome in oncohematological patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Swerdlow S.H.
        • Campo E.
        • Harris N.L.
        • Jaffe E.S.
        • Pileri S.A.
        • Stein H.
        • et al.
        WHO classification of tumours of haematopoietic and lymphoid tissues.
        4th ed. International Agency for Research on Cancer (IARC) 69372 Lyon Cedex 08, France2017
      1. Mitelman database of chromosome aberrations and gene fusions in cancer 2020.

        • Malcovati L.
        • Papaemmanuil E.
        • Ambaglio I.
        • Elena C.
        • Gallì A.
        • Della Porta M.G.
        • et al.
        Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia.
        Blood. 2014; 124: 1513-1521
        • Bains A.
        • Luthra R.
        • Medeiros L.J.
        • Zuo Z.
        FLT3 and NPM1 mutations in myelodysplastic síndromes.
        Am J Clin Pathol. 2011; 135: 62-69
        • Tefferi A.
        • Barbui T.
        Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management.
        Am J Hematol. 2019; 94: 133-143
        • Hirose Y.
        • Masaki Y.
        • Sugai S.
        Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases.
        Eur J Haematol. 2002; 68: 112-116
        • Tefferi A.
        • Lasho T.R.
        • Guglielmelli P.
        • Finke C.M.
        • Rotunno G.
        • Elala Y.
        • et al.
        Targeted deep sequencing in polycythemia vera and essential thrombocythemia.
        Blood Adv. 2016; 1: 21-30
        • McGowan-Jordan J.
        • A. Hastings R.J.
        • Moore S.
        ISCN, an international system for human cytogenomic nomenclature.
        Karger, 2020
        • Noguera N.I.
        • Ammatuna E.
        • Zangrilli D.
        • Lavorgna S.
        • Divona M.
        • Buccisano F.
        • et al.
        Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary electrophoresis in acute myeloid leukemia.
        Leukemia. 2005; 19: 1479-1482
        • Martínez-Serra J.
        • Maffiotte E.
        • Gutiérrez A.
        • Durán M.A.
        • Amat J.C.
        • Besalduch J.
        New real-time PCR-based method for the joint genotyping of JAK2 (V617F) with inherited thrombophilic F5 and F2 mutations.
        Clin Chim Acta. 2009; 410: 59-63
        • Sukhai M.A.
        • Craddock K.J.
        • Thomas M.
        • Hansen A.R.
        • Zhang T.
        • Siu L.
        • et al.
        A classification system for clinical relevance of somatic variants identified in molecular profiling of càncer.
        Genet Med. 2016; 18: 128-136
        • Uhrig S.
        • Ellermann J.
        • Walther T.
        • Burkhardt P.
        • Fröhlich M.
        • Hutter B.
        • et al.
        Accurate and efficient detection of gene fusions from RNA sequencing data.
        Genome Res. 2021; 31: 448-460
        • Schmidt B.M.
        • Davidson N.M.
        • Hawkins A.D.K.
        • Bartolo R.
        • Majewski I.J.
        • Ekert P.G.
        • et al.
        Clinker: visualizing fusion genes detected in RNA-seq data.
        Gigascience. 2018; 7: giy079
        • Groupe Français de Cytogénétique Hématologique
        Cytogenetics of acutely transformed chronic myeloproliferative syndromes without a Philadelphia chromosome. A multicenter study of 55 patients.
        Cancer Genet Cytogenet. 1988; 32: 157-168
        • Sano K.
        • Goji J.
        • Kosaka Y.
        • Nakamura H.
        • Nakamura F.
        • Tatsumi E.
        Translocation (10;12)(q24;q15) in a T-Cell lymphoblastic lymphoma with myeloid hyperplasia.
        Cancer Genet Cytogenet. 1998; 105: 168-171
        • Lundberg P.
        • Karow A.
        • Nienhold R.
        • Looser R.
        • Hao-Shen H.
        • Nissen I.
        • et al.
        Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms.
        Blood. 2014; 123: 2020-2028
        • Abdel-Wahab O.
        • Manshouri T.
        • Patel J.
        • Harris K.
        • Yao J.J.
        • Hedvat C.
        • et al.
        Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias.
        Cancer Res. 2010; 70: 447-452
        • Ikeda K.
        • Ogawa K.
        • Takeishi Y.
        The role of HMGA2 in the proliferation and expansion of hematopoietic cell in myeloproliferative neoplasms.
        J Med Sci. 2012; 58: 91-100
        • Santulli B.
        • Kazmierczak B.
        • Napolitano R.
        • Caliendo I.
        • Chiappetta G.
        • Rippe V.
        • et al.
        A 12q13 translocation involving the HMG1-C gene in Richter transformation of a chronic lymphocytic leukemia.
        Cancer Genet Cytogenet. 2000; 119: 70-73
        • Kottickal L.V.
        • Sarada B.
        • Ashar H.
        • Chada K.
        • Nagarajan L.
        Preferential expression of HMG1-C isoforms lacking the acidic carboxy terminal in human leukemia.
        Biochem Biophys Res Comm. 1998; 242: 452-456
        • Pierantoni G.M.
        • Santulli B.
        • Caliendo I.
        • Pentimalli F.
        • Chiappetta G.
        • Zanesi N.
        • et al.
        HMGA2 locus rearrangement in a case of acute lymphoblastic leukemia.
        Int J Oncol. 2003; 23: 363-367
        • Andrieux J.
        • Demory J.L.
        • Dupriez B.
        • Quief S.
        • Plantier I.
        • Roumier C.
        • et al.
        Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia.
        Genes Chrom Cancer. 2004; 39: 82-87
        • Odero M.D.
        • Grand F.H.
        • Iqbal S.
        • Ross F.
        • Roman J.P.
        • Vizmanos J.L.
        • et al.
        Disruption and aberrant expression of HMGA2 as a consequence of diverse chromosomal translocations in myeloid malignancies.
        Leukemia. 2005; 19: 245-252
        • Marquis M.
        • Beaubois C.
        • Lavallée V.P.
        • Abrahamowicz M.
        • Danieli C.
        • Lemieux S.
        • et al.
        High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia.
        Blood Cancer J. 2018; 8: 68
        • Sankunny M.
        • Eng C.
        Identification of nuclear export signal in KLLN suggests potential role in proteasomal degradation in cancer cells.
        Oncotarget. 2020; 11: 4625-4636
        • Wang Y.
        • Radhakrishnan D.
        • He X.
        • Peehl D.M.
        • Eng C.
        Transcription factor KLLN inhibits tumor growth by AR suppression, induces apoptosis by TP53/TP73 stimulation in prostate carcinomas, and correlates with cellular differentiation.
        J Clin Endocrinol Metab. 2013; 98: 586-594
        • Wang Y.
        • He X.
        • Yu Q.
        • Eng C.
        Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas.
        Hum Mol Genet. 2013; 22: 2263-2272
        • Hu K.
        • Liang M.
        Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN.
        In Vitro Cell Dev Biol Anim. 2017; 53: 149-156
        • Zou A.
        • Liu X.
        • Mai Z.
        • Zhang J.
        • Liu Z.
        • Huang Q.
        • et al.
        LINC00472 acts as a tumor supressor in NSCLC through KLLN-mediated p53-signalling pathway via microRNA-149-3p and microRNA-4270.
        Mol Ther Nucleic Acids. 2019; 17: 563-577
        • Nizialek E.A.
        • Peterson C.
        • Mester J.L.
        • Downes-Kelly E.
        • Eng C.
        Germline and somatic KLLN alterations in breast cancer dysregulate G2 arrest.
        Hum Mol Genet. 2013; 22: 2451-2461
        • Nyåkern M.
        • Tazzari P.L.
        • Finelli C.
        • Bosi C.
        • Follo M.Y.
        • Grafone T.
        • et al.
        Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients.
        Leukemia. 2006; 20 (Feb): 230-238
        • Liu Y.L.
        • Yan Y.
        • Webster C.
        • Shao L.
        • Lensing S.Y.
        • Ni H.
        • et al.
        Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy.
        Blood. 2016; 127 (Apr 14): 1912-1922