SCIENTIFIC PROGRAMME
SESSION I
THE GENOMIC AND
EPIGENOMIC LANDSCAPE
OF CLL AND CLINICAL
CONSEQUENCES
SESSION II
THE ROLE OF BCR
ACTIVATION AND
SIGNALLING FOR CLL
SESSION III
THERAPEUTIC OPTIONS
FOR CLL
SESSION IV
LONG TERM FOLLOW
UP OF CLINICAL TRIALS
VERSUS REAL WORLD
DATA (OUTSIDE CLINICAL
TRIALS DATA-OCT)
SESSION V
THE INCREASING ROLE
OF THE LEUKAEMIC
MICROENVIRONMENT
SESSION VI
THERAPEUTIC OPTIONS 2 :
THE USE OF CELLULAR
AND NON-CELLULAR
IMMUNOTHERAPIES IN
CLL
SESSION VII
EFFICACY THROUGH
SAFETY
SESSION VIII
CLONAL HETEROGENEITY,
CLONAL EVOLUTION AND
MECHANISMS OF DRUG
RESISTANCE
SESSION IX
CONTRASTING
THERAPEUTIC CONCEPTS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES
THE KRAB ZINC-FINGER PROTEIN ZNF224 IS A POTENTIAL PROGNOSTIC MARKER AND
THERAPEUTIC TARGET FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Elena Cesaroa, Rosa Catapanoa, Arianna Pastorea, Raffaele Sessaa, Marialuigia Iannalfob, Federico
Chiurazzib, Dario Bruzzesec, Michela Grossoa, Paola Costanzoa
aDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via
Pansini 5 80131, Naples, Italy
bDivision of Hematology, Department of Clinical and Experimental Medicine, University of Naples Federico
II, Via Pansini 5, 80131, Naples, Italy
cDepartment of Public Health, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
Objectives ZNF224 is a transcription factor belonging to the Kruppel-like zinc-finger protein
family, that may have dual functions in malignancies as both an oncogene or a tumor suppressor,
depending on the cellular and molecular context (1). In CLL ZNF224 exerts an oncogenic role,
contributing to apoptosis resistance and impaired cell growth through the transcriptional control
of cyclin D3. Previously, we had found that ZNF224 is expressed at high levels in CLL patients thus
suggesting ZNF224 as a novel prognostic factor in CLL (2). We now aimed to analyze correlations
between ZNF224 expression levels and disease progression in a large cohort of CLL patients, in
order to validate ZNF224 as prognostic biomarker in CLL.
Methods B lymphocytes were isolated from peripheral blood of CLL patients clinically classified
into indolent and aggressive groups. Total RNA was purified from cell samples to evaluate ZNF224
expression levels by quantitative RT-real time PCR analysis.
Results Molecular analysis performed on 60 CLL patients showed an interesting correlation
between high ZNF224 expression levels and disease progression. Furthermore, in a subgroup of
patients who were responsive to chemotherapy, we found that ZNF224 levels were lowered with
respect to pre-treatment conditions. These findings, along with our previous results (2), reinforce
the role of ZNF224 as prognostic factor and suggest that persistent high expression levels of
ZNF224 could trigger chemotherapy resistance, thus proposing ZNF 224 as a novel therapeutic
target in CLL.
Conclusions The presentation and course of CLL is highly variable. In some cases, the disease
presents with an indolent course whereas in in others the disease progresses with an aggressive
course (3). Therefore, the identification of novel prognostic factors may contribute to improve
the CLL classification and provide indications for treatment options. A better understanding of
overall outcames and landscape are also expected to identify novel terapeutic targets in CLL.
References
1. Cesaro, E., Sodaro, G., Montano, G., Grosso, M., Lupo, A., Costanzo, P. The Complex Role of the
ZNF224 Transcription Factor in Cancer. Adv. Protein Chem. Struct. Biol. 2017, 107, 191-222.
2. Busiello, T., Ciano, M., Romano, S., Sodaro, G., Garofalo, O., Bruzzese, D., Simeone, L.,
Chiurazzi, F., Romano, MF., Costanzo, P., Cesaro, E. Role of ZNF224 in cell growth and
chemoresistance of chronic lymphocitic leukemia. Hum Mol Genet. 2017, 15, 2344- 353.
3. Strati, P., Shanafelt, T.D. Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic
leukemia: diagnosis, natural history, and risk stratification. Blood 2015, 126, 454–462.
POSTER 2