Discussion
According to our knowledge, this is the first patient of AML with
translocation (x; 3) (q24; p13) to be described. Genetic analysis is
essential in classifying AML (5-7). Cytogenetic abnormalities are common
in 50% of patients with AML. Chromosome abnormalities are used to
classify patients with AML, regardless of blast count. The cytogenetic
analysis also reveals prognostic and therapeutic consequences
abnormalities, can help evaluate the response to therapy, and will
likely play a significant part in abnormality-tailored treatments in the
future. Likewise, mutational analysis is particularly vital in
diagnosing and treating AML (5).
Three distinct regions on the short arm of chromosome 3 have been
associated with tumorigenesis. One of the previously mentioned regions
is situated at the chromosomal locus 3p13~p14.2. (12).
Historically, this region has been identified as a common human
chromosomal problematic locus. (13)
It is hypothesized that the human chromosomal region 3p12-p23 contains
at least three tumor suppressor genes associated with lung cancer, renal
cell carcinoma(RCC), and other neoplasias. (14)(15)
A study was conducted in 2007 to examine the cytogenetic alterations in
38 instances of renal tumors in correlation with the histopathological
observations. The present study reveals that the structural
rearrangements observed in the 3p region were exclusive to clear cell
renal cell carcinoma (RCC). Notably, the translocation event between
chromosomes 3p13 and 5q22 was the most frequently observed structural
rearrangement in this context. (12) The early stages of tumorigenesis
are characterized by deletions occurring at the short arm of chromosome
3. (12)
Another study has demonstrated that the elimination of 3p13
characterizes a unique and forceful molecular subgroup of ERG-positive
prostate cancers, conceivably instigated by the deactivation of numerous
tumor suppressors. (16)
The gene FOXP1 displays broad expression across various adult tissues,
however, neoplastic cells frequently manifest a significant alteration
in the localization or level of FOXP1 expression. The genomic locus of
the human FOXP1 gene is situated on chromosome 3p13.
Forkhead box P1 is a transcription factor that regulates tissue and
cell-type-specific gene transcription during development and adulthood.
It has potential tumor suppressor properties and is located within a
tumor suppressor region. (17)
The involvement of FOXP1 has been observed in various physiological
contexts, such as the development of B-cells, differentiation of
monocytes, and regeneration of lung the epithelia. The gene in question
exhibits dual functionality in cancer, serving as both an oncogene in
B-cell lymphoma, ovarian cancer, and hepatocellular carcinoma, and a
tumor suppressor in T-cell lymphoma, NSCLC (Non-Small Cell Lung Cancer),
and colorectal cancer. (18-25)
Additionally, there exists supporting evidence indicating that the
expression of FOXP1 in cells affected by breast cancer helps reduce the
production of cytokines that attract T-cells, thereby preventing the
infiltration of stated cells. (18, 26)
FOXP1’s function in T-cells may lead to T-cell lymphoma. (18, 26)
In 2023 Zhenya Tang et al. identified 17 AML patients with a pericentric
inv(3) leading to MECOM rearrangement, one of them had breakpoints at
3p13 on 3p and 3q26.2 on 3q.(27)
45% of patients (N=5 of 11) in the study of Jelena D. Milosevic et al.
carried deletions mapping to the transcription factors FOXP1.(29)
Previous studies have demonstrated that specific translocations in acute
myeloid leukemia (AML) can predict response to therapy and overall
survival. For example, patients with AML and the t(15;17) translocation,
which results in the PML-RARA fusion gene, have a better response to
all-trans retinoic acid
(ATRA) therapy and a higher
overall survival rate compared to those without this translocation (8,
9). Similarly, patients with AML and the t(8;21) translocation, have a
more favorable prognosis than patients without this translocation (10,
11).
Katja Seipel et al. at 2020 concluded that in AML patients receiving
aggressive induction chemotherapy and autologous stem cell transplant,
FOXP1 predicts survival. Patients with high FoxP1 gene expression had
shorter progression-free and overall survival.(28)
Levavasseur et al. have shown that Cytogenetically normal AML patients
with high FOXP1 expression had worse survival. FOXP1 knockdown increased
superoxide anion levels, oxidizing cells and increased cellular
oxidative stress. (30)
This translocation may cause chemotherapy refractoriness in AML.
Unidentified companion gene mutations may also cause refractory illness.
Collecting and reporting uncommon chromosomal abnormalities may help
explain AML’s pathophysiology and prognosis. Early identification of the
disease during the clinical course may lead to better patient outcomes
and management in the future. This may facilitate the selection of
patients for more aggressive chemotherapy regimens and allogeneic stem
cell transplants.
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Table 1