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Do you know how ALCL is caused by T cell mutations?
Did you know that faulty T-cell proliferation can lead to a type of cancer called anaplastic large cell lymphoma (ALCL)? ALCL is a type of non-Hodgkin lymphoma characterized by abnormal proliferation of T cells and is considered a unified entity, especially in children. According to the Centers for Disease Control and Prevention, the incidence of ALCL in the United States is approximately 0.25 cases per 100,000 people.
ALCL can be classified into four types based on microscopic findings, and these types differ significantly in genetic abnormalities, prognosis, and treatments. The latest WHO classification system has updated it and divided it into ALK-positive ALCL, ALK-negative ALCL, primary cutaneous ALCL (pcALCL) and breast implant-associated ALCL (BIA-ALCL).
"ALK-positive and ALK-negative ALCL are both aggressive systemic lymphomas. The difference between them lies in the presence or absence of abnormal ALK protein."
ALK (non-small cell lung cancer related gene) is a protein located on the second chromosome. Its mutation leads to the production of abnormal proteins, further promoting cell proliferation. In ALK-positive ALCL, part of the ALK gene fuses with other genes to form an abnormal product called a "fusion gene." This fusion can lead to more ALK activity. This abnormal signaling triggers behaviors such as cell proliferation and survival that can promote malignancy.
Characteristics of ALK-positive large cell lymphoma
ALK-positive ALCL is most common in adolescents and young adults and usually presents when the disease has progressed to stage III or IV. Many patients experience systemic symptoms such as fever, night sweats, and weight loss, accompanied by swollen lymph nodes. The presence rate of tumor cells in bone marrow is as high as 40%.
"About 90% of young patients will produce autoantibodies against the ALK fusion protein."
Diagnosis and Treatment
The diagnosis of ALK-positive ALCL mainly relies on histology and immunological examination of tissues. Usually these tissues will show tumor-like infiltration and contain a variety of characteristic cells. For diagnosis, detecting the presence of ALC fusion proteins is critical. The treatment method includes the use of a combination of anti-CD30 antibodies and chemotherapy drugs, with remarkable results.
ALK-negative large cell lymphoma
In contrast, patients with ALK-negative ALCL are usually older and have predominantly lymph node disease. Although its prognosis is often considered worse than ALK-positive ALCL, this perception may be related to age at diagnosis and stage of disease progression. Recent studies have shown that the prognostic difference between the two is not necessarily as clear as previously observed.
Major cutaneous undifferentiated large cell lymphoma
pcALCL is one of the most common cutaneous lymphomas and usually appears as red bumps on the skin. The histological characteristics of the lesions show that there may also be characteristic "marker cells" in the tumor cells. Although this type of lymphoma progresses more slowly, in rare cases it may still metastasize to lymph nodes.
ALCL’s future direction
Currently, research on ALCL is still ongoing, especially the deepening understanding of its genetic and molecular characteristics, which provides a possible path for future personalized treatment. Treatment of ALCL varies depending on the patient's specific condition and includes strategies such as chemotherapy, targeted therapy, and stem cell transplantation.
As our understanding of ALCL deepens, will we be able to find breakthrough treatments for this cancer in the future?
