1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia

  • Giulia Daniele
  • Alberto L’Abbate
  • Antonella Turchiano
  • Orazio Palumbo
  • Massimo Carella
  • Crocifissa Lo Cunsolo
  • Paolo Iuzzolino
  • Angelo Lonoce
  • María Hernández-Sánchez
  • Carla Minoia
  • Patrizia Leone
  • Jesus Maria Hernandez-Rivas
  • Clelia Tiziana StorlazziEmail author
Case Report


The identification of chromosome 1 translocations and deletions is a rare and poorly investigated event in chronic lymphocytic leukemia (CLL). Nevertheless, the identification of novel additional molecular alterations is of great interest, opening to new prognostic and therapeutic strategies for such heterogeneous hematological disease. We here describe a patient affected by CLL with a mutated IGHV status, showing a balanced t(1;3)(q23.1;q21.3) translocation and a der(18)t(1;18)(q24.2;p11.32), accompanying the recurrent 13q14 heterozygous deletion in all analyzed cells at onset. By combining whole-genome sequencing, SNP array, RNA sequencing, and FISH analyses, we defined a 1q23.1 biallelic minimally deleted region flanking translocations breakpoints at both derivative chromosome 1 homologues. The deletion resulted in the downregulation of the Fc receptor-like family genes FCRL1, FCRL2, and FCRL3 and in the lack of expression of FCRL5, observed by RT-qPCR. The mutational status of TP53, NOTCH1, SF3B1, MYD88, FBXW7, and XPO1 was investigated by targeted next-generation sequencing, detecting a frameshift deletion within NOTCH1 (c.7544_7545delCT). We hypothesize a loss of tumor suppressor function for FCRL genes, cooperating with NOTCH1 mutation and 13q14 genomic loss in our patient, both conferring a negative prognosis, independently from the known biological prognostic factors of CLL.


CLL 1q23.1 deletion FCRL IGHV NOTCH1 Translocation 


Authors’ contribution

GD and AT performed and analyzed FISH, M-FISH, RT-PCR, and RT-qPCR experiments. AL’A analyzed WGS and RNA-Seq data. OP and MC performed and analyzed SNP array data. CLC and PI performed cytogenetic examinations and flow cytometry immunophenotyping. AL and PL performed and analyzed RT-PCR experiments. MHS and JMHR performed and interpreted mutational analysis. CM and JMHR analyzed and explained the patient data regarding the hematological disease. CTS conceptual organized and supervised the experiments. GD, AL’A, AT, MHS, and CTS were major contributors in writing the manuscript. All authors read and approved the final manuscript.


This work was supported by the AIRC (Associazione Italiana per la Ricerca sul Cancro; AIRC IG No. 15413 for CTS).

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Giulia Daniele
    • 1
  • Alberto L’Abbate
    • 1
  • Antonella Turchiano
    • 1
  • Orazio Palumbo
    • 2
  • Massimo Carella
    • 2
  • Crocifissa Lo Cunsolo
    • 3
  • Paolo Iuzzolino
    • 3
  • Angelo Lonoce
    • 1
  • María Hernández-Sánchez
    • 4
  • Carla Minoia
    • 5
  • Patrizia Leone
    • 6
  • Jesus Maria Hernandez-Rivas
    • 4
  • Clelia Tiziana Storlazzi
    • 1
    Email author
  1. 1.Department of BiologyUniversity of Bari “Aldo Moro”BariItaly
  2. 2.Medical Genetics UnitIRCCS Casa Sollievo della Sofferenza HospitalSan Giovanni RotondoItaly
  3. 3.UO Anatomia Patologica, Ospedale S. MartinoBellunoItaly
  4. 4.Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del CáncerUniversidad de Salamanca, CSICSalamancaSpain
  5. 5.Haematology UnitIRCCS Istituto Tumori “Giovanni Paolo II”BariItaly
  6. 6.Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. BaccelliUniversity of Bari Aldo Moro Medical SchoolBariItaly

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