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Tumor Discovery FBXW7 in Leukemia

state, unable to complete normal differentiation programs, Key oncogenes and tumor suppressors, such as NOTCH1
and continue to proliferate in the bone marrow, peripheral in T-ALL and Breakpoint Cluster Region–Abelson (BCR–
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blood, and other tissues. This abnormal proliferation is ABL) in CML, are implicated in the development and
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driven by dysregulated cell cycle control, differentiation progression of these malignancies. Understanding the
inhibition, and enhanced self-renewal ability. For example, molecular landscape of leukemia has enabled more precise
certain leukemia cells acquire specific mutations that diagnostic tools and targeted therapies.
disrupt negative feedback regulation of proliferation,
further exacerbating uncontrolled cell division by altering 1.2. Leukemia in China: Incidence and risk factors
cyclin expression or activating abnormal signaling In China, leukemia remains a major public health issue,
pathways. In addition, these leukemia cells typically lack particularly affecting children and young adults. 23,24 The
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the ability to respond to death signals, allowing them to high incidence of leukemia, along with challenges in early
evade apoptosis and enhance their survival within the diagnosis and treatment, poses complex health threats
body. The unchecked proliferation of leukemia cells to this population. Due to the incomplete development
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breaks through normal regulatory mechanisms, leading to of the immune system in children and young people,
the accumulation of large numbers of leukemia cells in the coupled with susceptibility to environmental pollution,
blood, disrupting hematopoiesis, and triggering a series of genetic factors, and other influences, the incidence of
clinical symptoms, including anemia, thrombocytopenia, leukemia is especially prominent in this group. Recent
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and neutropenia, which manifest as fatigue, bleeding epidemiological data indicate that the annual incidence
tendencies, and increased susceptibility to infections. of leukemia is approximately 3 – 4 cases per 100,000
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Since normal hematopoietic cells in the bone marrow people, with ALL being the most common cancer
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are replaced by leukemia cells, the patient’s immune among children, peaking between the ages of 2 and 5.
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function is severely compromised, making them highly In adults, the incidence of AML and CLL is relatively
susceptible to bacterial, viral, and other infections, further higher. Leukemia has become one of the leading causes
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exacerbating the condition. Therefore, the treatment of of cancer-related deaths among children and young adults
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leukemia requires not only controlling the proliferation in China. This phenomenon highlights the urgent need for
of leukemia cells but also restoring the normal function of improvements in early diagnosis, effective prevention, and
the hematopoietic system, alleviating the patient’s clinical treatment strategies for leukemia, to reduce the disease
symptoms, and improving their quality of life and survival burden and improve patient survival rates.
rate. Multiple factors are associated with the etiology of
Leukemia is broadly classified based on the lineage of leukemia, including genetic susceptibility, environmental
the affected hematopoietic cells (myeloid or lymphoid) exposures (e.g., radiation, benzene, and pesticides),
and the degree of cellular maturity (acute or chronic). The and viral infections. For instance, exposure to ionizing
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most common types of leukemia include (Figure 1): radiation or chemical carcinogens has been linked to
(i) Acute myeloid leukemia (AML) : Characterized by increase leukemia risk. Genetic predisposition also
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the rapid accumulation of immature myeloid blasts in plays a role, with certain inherited disorders, such as Li–
the bone marrow. 10 Fraumeni syndrome and Fanconi anemia, predisposing
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(ii) Acute lymphoblastic leukemia (ALL) : Involves individuals to leukemia. In addition, viral infections such
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immature lymphoblasts and is more common in as Epstein-Barr virus and human T-cell lymphotropic
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children. ALL can be further subdivided into T-cell virus type 1 have been implicated in the development of
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ALL (T-ALL) and B-cell ALL (B-ALL). 14 leukemia.
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(iii) Chronic myeloid leukemia (CML) : Typically
progresses from a chronic phase with more mature 1.3. Molecular pathogenesis of leukemia
myeloid cells to a more aggressive blast crisis. 16 Leukemia arises from the accumulation of genetic
(iv) Chronic lymphocytic leukemia (CLL) : A slow- mutations and chromosomal abnormalities that disrupt
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growing leukemia of more mature lymphocytes, normal cell signaling pathways, cell cycle checkpoints, and
commonly affecting older adults. apoptosis. These genetic lesions often involve oncogenes,
The clinical manifestations of leukemia include fatigue, tumor suppressor genes, and epigenetic regulators, which
recurrent infections, easy bruising, and bleeding, caused by collectively drive the clonal expansion of leukemic cells.
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the impaired production of normal blood cells. Advances For example, BCR-ABL, generated by the t(9;22)
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in molecular diagnostics have revealed a wide array of chromosomal translocation, is a characteristic marker
genetic mutations driving the various leukemia subtypes. of CML. The BCR-ABL fusion protein possesses
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Volume 4 Issue 3 (2025) 2 doi: 10.36922/TD025150027