POSTER 8
CLONAL EVOLUTION OF MPN: A CASE REPORT
Rita S. Gomes1, Sara Duarte1, Diana Mota1,2, Ana T Simões1, Margarida Coucelo1, José Carda1 and
Letícia Ribeiro1
(1)Coimbra University Hospital Centre, Coimbra, Portugal
(2)District Hospital of Figueira da Foz, Figueira da Foz, Portugal
Introduction: Myeloproliferative neoplasms (MPN) are characterized by clonal
hematopoiesis, most frequently with driver mutations in JAK2, CALR and MPL genes.
However, with the advent of next-generation sequencing (NGS) techniques, mutations in
other clonal hematopoiesis-related genes have been identified.
Aim: To report a case of clonal evolution in MPN and demonstrate the role of NGS in its
diagnosis, prognosis and therapeutic approach.
Methods: Patient´s (pt) clinical file consultation. DNA mutational analysis recurring to NGS
myeloid custom panel (ThermoFisher).
Case report: Man, 54 years old, firstly observed in August/2015 for persistent thrombocytosis
(platelets 857G/L). Although asymptomatic, the patient had recently an acute myocardial
infarction. Cytogenetic studies revealed a normal karyotype (46, XY), molecular studies
showed a JAK2 V617F mutation and bone marrow (BM) biopsy was compatible with an
essential thrombocytosis (ET) diagnosis. The patient was medicated with hydroxycarbamide,
with good control of thrombocytosis and no toxicities. In March/2017, due to disease
progression (leukocytosis 25 G/L, neutrophilia 84.9%, <10% of myeloid precursors in
peripheral blood, monocytosis 1.5 G/L, Hb11.1g/dL and LDH), a BM re-evaluation was
performed. Pt had progressed to prefibrotic myelofibrosis (MF) and karyotype reveled clonal
evolution (46,XY16/46,XY,+8-192/47,XY,+82). At this time, mutational profiling was
undertaken applying NGS (table 1), which showed a complex mutational spectrum, including
ASXL1/EZH2/ETNK1/CSF3R mutations and absence of JAK2 V617F mutation. The retrospective
study revealed the presence of additional mutations in ASXL1/EZH2/ETNK1/CSF3R at the time
of diagnosis. In August/2017 he aggravated clinical and analytically (leukocytosis 60G/L,
neutrophils 77%, 11% precursors, 1% blasts, Hb11g/dL, platelets 280G/L, LDH 901U/L (<241))
with evolution to MF with overt fibrosis.
Noteworthy, karyotype presented additional alterations 47,XY,+8,del20(q11.2;q12) 6/46,
XY, del20(q11.2;q12)6/46XY,+83/46,XY5 and NGS showed 2 additional mutations
in TP53 gene. Pt started Ruxolitinib in October/2017, however, while awaiting for allogenic
transplant, the disease progressed to acute myeloid leukemia and the pt died.
Conclusion: We present a case of ET JAK2 V617F positive with clonal evolution to acute
myeloid leukemia. The retrospective molecular study applying an NGS myeloid panel,
demonstrated that at the time of diagnosis the patient already harbored additional mutations
that expanded and drove clonal and disease evolution. The remission JAK2V617F positive
clone and the presence of CSF3RQ776X and CSF3RT618I mutations, reported in patients with
neutrophilic leukemia chronic/atypical chronic myeloid leukemia, may justify disease
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES