The Swiss Society of Medical Oncology (SGMO), the Swiss Society of Hematology (SGH) and the Swiss Group for Clinical Cancer Research (SAKK) come together at the annual Swiss Oncology & Hematology Congress to share the latest research findings in their respective fields. This year’s motto was “Overcoming borders together”.
ASPP2 is a tumor suppressor that regulates key proteins such as p53, Bcl-2 and NFkB to control key cancer-related signaling pathways. ASPP2 contains a highly conserved Ank-SH3 domain at its C-terminus that mediates these interactions. A previously unknown oncogenic isoform known as ASPP2k has now been discovered, which is very common in cancer. This dominant-negative mutant has lost the crucial C-terminus and inhibits ASPP2-WT function, resulting in loss of tumor suppressive capabilities. ASPP2k was first discovered in acute leukemias, but screening of multiple tumor entities revealed frequent expression of ASPP2k in cancers associated with more aggressive tumor biology and resistance to therapy [1]. More than 500 tumors, including AML, glioma, sarcoma, breast, colon and lung cancer, were examined for their ASPP2k expression. ASPP2k was stably suppressed or overexpressed in cell lines from these entities and in patient tissue. Depending on ASPP2k, the induction of apoptosis, cell proliferation, migration, invasion, colony formation, telomere length, angiogenesis and related signaling pathways were analyzed.
The expression of ASPP2κ was confirmed in practically all patients. ASPP2κ-expressing TNBC cell models showed reduced induction of apoptosis (average IC50s -30%), higher proliferation (average +25%), migration (average +65%) and invasion rates (average +70%). The elimination (KD) of ASPP2k sensitized the cells to chemotherapy and/or γ-irradiation. Xenotransplanted ASPP2κ-KD tumor mouse models confirm attenuated tumor seeding, reduced growth and metastasis, resulting in significantly prolonged overall survival.
Myeloma, lymphoma or monoclonal B-cell lymphocytosis?
The correct diagnosis of hematologic malignancies is often difficult. An integrative approach can then be expedient [2]. A 66-year-old, otherwise healthy woman presented with dyspnea, angina pectoris and fatigue. There were no signs of bleeding or fever. She reported a weight loss of 6 kg in 12 months. The blood values showed normal white blood cells, a normocytic, normochromic, hyporegenerative anemia (hemoglobin 6.1 g/dl), a slight thrombocytopenia of 89 G/L and a slightly elevated LDH (236 U/L). Immunofixation showed a biclonal gammopathy IgG lambda and IgM kappa. No lymphadenopathy or organomegaly was observed in the CT scan, nor was any osteolysis. Bone marrow cytology showed increased lymphocytes with suppression of normal hematopoiesis, with suspected lymphoma infiltration. Immunophenotyping revealed a mature B-cell population with expression of CD20, CD22 and CD79b. The results are consistent with marginal zone lymphoma of the spleen. In addition, a monoclonal B-cell population was found. The FISH examination revealed a 13q14 deletion. Molecular biology revealed a MYD88 and TP53 mutation. On the other hand, BM histology showed a clear infiltration with a biclonal myeloma. It is assumed that the patient has three hematologic malignancies: plasma cell myeloma, mature non-Hodgkin’s lymphoma and a monoclonal B-cell lymphocytosis of the B-CLL type. A therapy was therefore started that targets both the myeloma and the lymphoma. As an accurate diagnosis can be challenging, an integrative approach including cytomorphology, histology, immunophenotyping, cytogenetics and molecular biology is essential.
Absorbing psychological stress
The cancer diagnosis and treatment lead to somatic symptoms and a high level of suffering for those affected, and in around 30% of cases to chronic psychological disorders. There is currently no published data on the frequency of psychological stress in oncology patients at the start of rehabilitation in Switzerland. As part of a prospective study, psychological distress at the start of oncological rehabilitation was recorded and compared with sociodemographic and clinical data [3]. In 296 of 400 patients, psychological distress was assessed using the German version of the 11-scale NCCN distress thermometer.
The average psychological stress in the collective was significantly increased at 5.8, and significantly increased stress values were found in 74.0% of patients. There was also a significant difference depending on gender. While younger women showed higher levels of distress than older patients (81.4% vs. 78.8%), older men showed higher levels of distress than younger men (71.4% vs. 64.3%). The subgroup with the highest distress scores were breast cancer patients, although the proportion of chronic disease stages was significantly lower compared to other tumor entities. However, the affected patients reported significant fatigue-like symptoms.
The authors conclude that the frequency of psychological problems at the beginning of oncological rehabilitation is extremely high. For this reason, active attention should generally be paid to the presence of psychological stress at the beginning of rehabilitation and psycho-oncological support should be further expanded in oncological rehabilitation.
Congress: Swiss Oncology and Hematology Congress (SOHC) 2023
Literature:
- Kampa-Schittenhelm K, et al: Detection and Characterization of ASPP2kappa(k) – a central hub of tumorigenesis and drug resistance. Abstract 188. Swiss Medical Weekly 2023;153 (Suppl. 274): 11.
- Medinger M, et al: Is it myeloma, lymphoma, or monoclonal B cell lymphocytosis? Or all of them? The need of an integrative diagnosis: a case report. Abstract 256. Swiss Medical Weekly 2023;153 (Suppl. 274): 69.
- Hass HG, et al: Incidence and predictive factors for psychological distress in cancer patients in Switzerland during oncological rehabilitation. Abstract 160. Swiss Medical Weekly 2023;153 (Suppl. 274): 57.
InFo ONKOLOGIE & HÄMATOLOGIE 2023, 11(6): 28 (published on 17.12.23, ahead of print)
