Supervisors info:
Μ. Κουτσιλιέρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γ. Βαϊόπουλος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κ. Σαμπάνη, Ερευνήτρια Α΄, ΙΠΡΕΤΕΑ, ΕΚΕΦΕ "Δημόκριτος"
Summary:
Introduction: Chronic Myelogenous Leukemia (CML) is defined by the Philadelphia
chromosome (Ph) as a result of t(9;22)(q34;q11.2) and the generation of BCR-ABL1
fusion gene. Variant translocations are found in 5-10% of patients with newly
diagnosed CML. They can be present either in a simple form, involving 22q11 and
one additional breakpoint, or in a complex form, involving 22q11, 9q34 and at least
one additional breakpoint. In variant translocations, the distribution of breakpoints
exhibits a nonrandom pattern. Although the clinical and hematological features of
these cases are not distinct from those seen in standard t(9;22), however, the
prognostic role of each individual variant translocation and its additional
chromosomal abnormalities has not been elucidated yet.
Purpose: The aim of this study is to determine the type and the frequency of variant
Ph translocations, their additional chromosomal abnormalities and involvement of
new breakpoints in a large Greek cohort of CML patients.
Material and Methods: The study included 809 newly diagnosed CML patients.
Among them, 48 (31 males, 17 females) exhibited a variant translocation in their
karyotype (5.9 %).
Results: A simple variant was found in 13 and a complex in 35. The most frequent
variant was t(17;22)(p13;q11) (n=2). Additional chromosomal abnormalities were
observed in 12 out of 48 patients: -Υ (n=1), +Ph (n=1), i(17)(q10) (n=1), +21 (n=2),
+22 (n=2) and other aberrations in 5 patients. Fourteen out of 48 variant
translocations have not been reported previously and four of them exhibited
involvement of new breakpoints: 3p27 (n=1), 5q15(n=1), 5q21-22 (n=1), 14p11 (n=1).
The most common chromosomes participated in variant translocations were: 2
(6/48), 11 (5/48) and 17 (5/48). There was no participation of the chromosomes Υ,
13, 16, 18 and the homologous 22.
Conclusions: Variant translocations were found in 5.9% of patients with newly
diagnosed CML, more commonly with complex form. Four of variant translocations
exhibited involvement of new breakpoints. The prognostic role of each individual
variant translocation and its additional chromosomal abnormalities has not been
elucidated yet. Conventional cytogenetic analysis is the only appropriate
methodology for the identification of variant translocations in CML. Reviewing of
cytogenetic data during each patient’s course of the disease is expected to point out
the role of certain variants and additional abnormalities in prognosis.
Keywords:
CML, Variant Ph, Chromosome Ph, Karyotype
