AMPLIFICATION OF c-MYC AND MLL GENES
AS A MARKER OF CLONAL CELL PROGRESSION
IN PATIENTS WITH MYELOID MALIGNANCY
AND TRISOMY OF CHROMOSOMES 8 OR 11
Angelova S1,*, Jordanova M2, Spassov B1, Shivarov V1, Simeonova M3,
Christov I4, Angelova P3, Alexandrova K5, Stoimenov A1, Nikolova V1,
Dimova I6, Ganeva P1, Tzvetkov N4, Hadjiev E5, Toshkov S1
*Corresponding Author: Svetlana Angelova, Biologist, Laboratory of Cytogenetics and Molecular Biology,
National Specialized Hospital for Active Therapy of Hematological Diseases, 6, «Plovdivsko pole», Sofia, 1756,
Bulgaria; Tel.: +35929701133; Fax : +35929701107; E-mail: sv_angelru@abv.bg
page: 17
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RESULTS
Solely Tri- or Tetrasomy 8. In nine of 18 patients
with an additional chromosome 8, this aberration was
an isolated clonal anomaly in the karyotype: seven patients
with +8 and two patients with tetrasomy 8. The
FISH analysis does not show significant amp c-MYC
in cases 1 through 7 (Table 1). In the karyotype of patients
1 to 4, the +8 aberration occurred in a minor cell
clone (from 10 to 33% of the analyzed metaphases).
Correlation between the number of c-MYC fluorescent
signals in the interphase nuclei and the cytogenetically
detected +8 metaphases in the first four patients showed
absence or no significant proliferative advantage of the
aberrant cell clone. In cases 5 to 7, the cell clone with
the +8 anomaly had a proliferative advantage. Only
two of our patients with solely +8 and without amp
c-MYC have achieved a hematological remission. The
other two patients from this group did not receive optimal
dose chemotherapy due to complications during
the neutropenic phase.
In patients 8 to 10, a karyotype progression from
tri- to tetrasomy 8 or from partial clonality to total expansion
of the aberrant cell clone was observed. Tetrasomy
8 in these cases was accompanied by amp c-
MYC. In two patients with MDS and expansion of the
cell clone harboring +8 and amp c-MYC, the disease
evolved to AML.
Trisomy 8 in the Karyotype With Additional
Aberrations. Seven of eight patients (11 through 17)
with +8 and additional chromosome aberrations, had
a different level of amp c-MYC: two with low (under
10%) and five with more than 10%. Coincidence of
composite chromosome anomalies and amp c-MYC
in most of the cases correlate with transformation of
MDS to AML and short survival (about 3 months)
without achieving a hematological remission. Only
one of the patients (17) with MDS-RARS (refractory
anemia with ring sideroblasts) and low level of amp
c-MYC, had comparatively long (13 months) overall
survival (OS) despite of his advanced age.
In conclusion, a different level of amp c-MYC was
observed in 12 of 18 (66.7%) patients with +8. The
karyotypes of patients with a significant level of amp
c-MYC demonstrated progressive chromosome complications.
Trisomy 11 and Suspicion of Amp MLL Complex
Karyotype. In two of the six cases with total or
partial +11 expansion of the affected cell clone was
observed. In four cases, a significant amp MLL was
recorded. Two patients with +11 (5 and 6) did not have
a significant amp MLL (Table 2). The median OS in
the patient group with the low level of amp MLL was
longer than that of the other patients with +11 (6 vs. 2
months. respectively).
In the two cases with suspected amp MLL and
complex karyotype and rearrangements on chromosome
11, there were low, 6% and significant, 67%,
levels of the amp MLL. Both had very short OS due
to early death in induction. All patients with amp MLL
and/or +11 did not achieve remission and had short
survival times.
In conclusion, all our patients with +11 demonstrated
a different level of amp MLL. The significant
level of amp MLL in this group is correlated with a
very short OS.
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