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Molecular Genetics of Chronic Lymphocytic Leukemia in Taiwan: Clinical and Pathogenetic Implications
Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western world. CLL belongs to the indolent lymphoma category, but its clinical course varies widely. During the preceding three decades,
many clinical and molecular features have been identified as predictors of outcome or of response to therapy. These molecular and clinical markers of CLL have greatly improved
our understanding of the biology of this disease and contributed to the optimization of individual patients’ management options. CLL is much less prevalent in Asia; it is viewed as a “Western disease”, and most knowledge about CLL is derived from studies in Western populations.
This knowledge gap has become particularly significant since our prior studies have shown
less favorable outcomes of CLL in Taiwan than those in the West. Thus, any differences in biological characteristics that may underlie
this disparity in the prognosis of CLL in Asian populations relative to Western populations
would be of great interest and value.
In collaboration with Professor Paolo Ghia at
Università Vita-Salute San Raffaele and
Istituto
di Ricovero e Cura a Carattere
Scientifico
(IRCCS) Istituto Scientifico San Raffaele, Milano, Italy, as well as Professor Liang-In Lin at the Department of Clinical Laboratory Science and Medical Technology, College of Medicine, National Taiwan University, Professor Hwei-Fang Tien and Dr. Shang-Ju Wu conducted the
current study, which sought to characterize and validate clinical implications of CLL immunogenetic and genetic features in a cohort of Taiwanese CLL patients, to highlight any potential geographical differences that may underlie the aforementioned outcome disparity. W
e found that the
IgHV
gene repertoire in this cohort was biased and distinct from that observed in Western cohorts, with the most common
IgHV
genes being
IgHV3-23
,
IgHV3-7,
and
IgHV3-48
(Figure 1A and 1B). T
he
observed differences in
IgHV
properties suggest that different pathogenetic factors are involved in
the development of CLL.
With respect to the mutational status of the
IgHV
gene, 63.8% of the patients carried mutated rearrangements, whereas 22.4% of the patients were
assigned to stereotyped subsets (with 6.9% and 15.5% of the patients assigned to major and minor subsets, respectively).
The frequencies of
NOTCH1, SF3B1, BIRC3
and
MYD88
mutations were 9.6%, 7.2%, 1.2%, and 2.4%, respectively; however, the frequency of
TP53
mutation
was significantly higher (20.5%) in our cohort than that in Western cohorts (Figure 2A and 2B). This high
TP53
mutation frequency could partially explain the dismal outcomes of patients with CLL in Taiwan.
The current study revealed immunogenetic and genetic features of Taiwanese CLL patients and the clinical implications of these features and highlighted geographical differences that may underlie the outcome disparity between Taiwanese and Western CLL patients. This knowledge could lead to the refinement of management strategies for Taiwanese CLL patients.
Figure 1. (A) Frequencies of
IgHV
subgroups and somatic hypermutation statuses in Taiwanese CLL patients.
(B) Comparison of
frequencies of
IgHV
gene usage
in Western and Taiwanese CLL patients
.
Figure 2. (A) Gene mutation and cytogenetic aberrancy statuses;
each column represents an untreated CLL case in the current study.
(B) Frequencies of common gene mutations in Taiwanese and Western CLL patients.
Reference
Shang-Ju Wu, Chien-Ting Lin, Andreas Agathangelidis, Liang-In Lin, Yuan-Yeh Kuo, Hwei-Fang Tien, and Paolo Ghia (
2017)
. Distinct Molecular Genetics of Chronic Lymphocytic Leukemia in Taiwan: Clinical and Pathogenetic Implications.
Haematologica,
102
(6):1085-1090
. DOI:10.3324/haematol.2016.157552.
Clinical Assistant Professor Shang-Ju Wu
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital
wushangju@ntu.edu.tw
Professor Hwei-Fang Tien
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital
hftien@ntu.edu.tw
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Molecular Genetics of Chronic Lymphocytic Leukemia in Taiwan: Clinical and Pathogenetic Implications
Keywords
chronic lymphocytic leukemia
molecular genetics
Taiwan
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