Double Minute Chromosomes Associated with Philadelphia Chromosome
in Meyloid Leukemia. A Case Study
Abolfazl Movafagh1*, Mostafa Rezaei Tavirani2 and Mohamad Hasan Heidari3
1Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Department of Medical Anatomy, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
*Corresponding author:
Abolfazl Movafagh, Ph.D
Associate Professor
Department of Medical Genetics
Faculty of Medicine
Shahid Beheshti
University of Medical Sciences
Tehran, Iran Fax: +98(21) 2240067 +98-21-
23872572 E-mail: Movafagh_a@yahoo.com
Received March 24, 2012; Accepted May 28, 2012; Published May 30, 2012
Citation: Movafagh A, Tavirani MR, Heidari MH (2012) Double Minute
Chromosomes Associated with Philadelphia Chromosome in Meyloid Leukemia.
A Case Study. J Cancer Sci Ther 4: 144-145. doi:10.4172/1948-5956.1000129
The Philadelphia chromosome was the first consistent cytogenetic abnormality observed in a human cancer.
Several characteristic chromosome rearrangements like double minute chromosomes are known to be associated
with different subtypes of myeloid leukemia. Double Minute Chromosomes are the cytogenetic hallmarks of genomic
rearrangements in cancers. Two cases, one with AML-M1 and the other with CML- blast crisis, associated with
double minute chromosomes and Philadelphia chromosome is presented. The additional chromosome changes to
primary chromosome abnormality may be influenced by other factor like chemotherapy. The identification of two
new cases with co-expression of double minute chromosomes and Ph chromosome presented here for the first time
in Iran together with large Mitelman database and other pertinent website reports is discussed.
Keywords
Co-expression; Ph; DM; Leukemia; Incidence
Introduction
Double minute chromosomes (DMs) were first described in a direct
preparation of cells from patient with untreated brochogenic carcinoma
[1]. Sait et al. [2] reported for the first time that, DMs originating from
chromosome 1. Double Minute Chromosomes are the cytogenetic
hallmarks of genomic amplification in cancers [3]. Furthermore,
DMs derived from the breakpoint region of translocation event [4].
Although DMs found in a variety of human tumor cells, their presence
in hematologic malignancies is rare. Also their role in leukemogenesis
is not clear but they have been reported to be associated with rapid
progression and short survival time [5]. Double Minute Chromosomes
are thought to be involved in tumorigenesis and in drug resistance
[6]. They are small chromatin particles that represent a form of extra
chromosomal gene amplification [7].
The Philadelphia (Ph) chromosome, or t(9;22) is the hallmark
of Chronic Myelogenious Leukemia (CML) [8] and acute myeloid
leukemia [5]. The Ph generally appears as a primary at the onset of the
disease. However, a late –developing or DMs has also been observed in
rare cases of CML [9] and AML [5].
Here we present two leukemia cases revealed double minute
chromosomes associated with Ph chromosome.
Case Report
Two patients with CML and AML have seen between 1994-2010,
from Shahid Beheshti University of Medical Sciences and various
private clinics, Tehran, Iran.
Case 1
A 23 years old housewife, in previous good health, presented with
weight loss, tiredness with a history of weakness with 3 months medical
treatment on chemotherapy. Her peripheral blood hemoglobin
was 6.2 g/dl with a platelet count of 100 × 109/l (differential: 77%
blast, 1% neutrophils, 22% lymphocytes). The marrow aspirate was
cellular with reduction in all normal marrow elements and marked
increased in Sudan Black-positive myeloblast. Peripheral blood and
bone marrow sample was submitted for chromosome analysis after 3
months from her initial chemotherapy. G-banding analysis in patient
one, AML-M1 showed that all of 20 metaphases cells revealed both
numerical and structural abnormalities, including 46,XX,t(9;22) +
dmin; 45,XX,t(9;22), -15 (Figure 1A). Sixteen of the 20 cells (80%) also
had 3-19 DMs in each cells. Her past medical history was no history of
prior toxic exposure.
Figure 1: Giemsa staining bone marrow cell containing dmin in the metaphase
of chronic and acute myeloid leukemia patients.
Case 2
In patient two, with CML- blast crisis, 28 years old female was
admitted to our hospital because of leukocytosis and anemia. On
admission also splenomeghaly was found, WBC 15.1 × 104 /mm3,
hemoglobin was 7.2 g/dl, RBC 224 × 104 /mm3 and bone marrow
examination revealed hypercellularity with promyelocyte 14.2% and
myeloblast 49.7%. She was presented at the time of cytogenetic study with intensive chemotherapy for 4 months. The patient smoked
cigarettes for about 7 years. G-banding analysis revealed that 14 of
the 20 metaphases cells (70%) had Ph chromosome + dmin (Figure
1B). Her past medical history was notable only for occupation for
cultivation as Farm Yard Manure. Fluorescence in situ Hybridization
(FISH) analysis was not performed for both cases. Because of the lack
of our patients response and / or shorter survival, did not allow us to
identify whether Ph chromosome was a primary or a secondary event.
Discussion
As part of the large population base study have been published
previously on CML and AML from own findings [10-13], the presence
of DMs and Ph chromosome together, with two leukemia patients were
identified in our laboratory was also observed in other parts of the world
(http://cgapanci.nih.gov/chromosomes/Mitelman) [5]. These two new
cases of DMs chromosome presented here is discussed in the following
report [12], and utilizing the largest chromosome aberrations database
in cancers (http://cgapanci.nih.gov/chromosomes/Mitelman). Also,
Thomas et al. [5] documented 33 cases with DMs in acute myeloid
leukemia in the current literature.
Chronic myelogenous leukemia is characterized by the Philadelphia
chromosome which originated by reciprocal translocation t (9;22) [8].
The Ph chromosome generally appears as a primary changes at the onset
of the disease. However, a late – developing or additional chromosome
abnormality has been observed in rare cases of CML [9], AML [5,14] .
The relationship of DMs and malignancies seems well established
and indeed DMs have not, so far, been observed in non malignant
cell [3]. Double minute chromosomes have been found in various
solid tumors, such as Colon, Pancreatic, Breast carcinoma, Brain
tumors, and Neuroblastoma (http://cgapanci.nih.gov/chromosomes/
Mitelman). However, it appears to be less common in AML [5].
Past medical history of both cases presented here, recorded without
history of any micro organism contaminations, but with the history
of anemia. In a case 2, past medical history was notable only for
occupation for cultivation as farm yard manure. It is coincident with
previous reports indicating that, DMs do occur in leukemic patients
without previous history of malignancy [15]. On the contrary, a relation
between DMs and previous mutagenesis exposure has been suggested
by some workers [16]. Thus for, suggest that the demonstration of DMs
in patients with AML might be an indication that such patients have
a previous history of malignant disease treated with irradiation or
chemotherapy or both [16]. Expression of Ph chromosome may have
been the first event in early myeloid stem cells in both of our patients,
with the dmin occurring later due to the treatment with chemotherapy.
The identification of two new cases of DMs associated with Ph
chromosome presented here are secondary. However, further studies
and accumulation of new cases are needed in the hope of defining it as
specific abnormalities in the field of leukemia.
Acknowledgements
I thanks, Dr. Fatemeh Isfahani, Dr. Abbas Hajfathali, Dr. Hamid Attarian, Dr.
Morteza Ghadiani, Dr. Hamid Rezvani; Departments Medical Oncology, Internal
Medicine. Thanks to Miss Niloofar Safavi for excellent technical assistance and
material collection. This article is the part of thesis work.
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