Cancer Research and Treatment

Original Articles

Hematologic malignancy

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia: Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim; Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1407

Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP^in-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

Citations

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Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
Li‐Xin Wu, Ming‐Yue Liao, Ming‐Yue Zhao, Nan Yan, Ping Zhang, Li‐Xia Liu, Jia‐Yue Qin, Shan‐Bo Cao, Jia Feng, Qian Jiang, Ying‐Jun Chang, Lan‐Ping Xu, Xiao‐Hui Zhang, Xiao‐Jun Huang, Hao Jiang, Hong‐Yu Zhang, Guo‐Rui Ruan
British Journal of Haematology.2025;[Epub] CrossRef
CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef
CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef
Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef

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Treatment Outcomes of Rituximab Plus Hyper-CVAD in Korean Patients with Sporadic Burkitt or Burkitt-like Lymphoma: Results of a Multicenter Analysis: Junshik Hong, Seok Jin Kim, Jae-Sook Ahn, Moo Kon Song, Yu Ri Kim, Ho Sup Lee, Ho-Young Yhim, Dok Hyun Yoon, Min Kyoung Kim, Sung Yong Oh, Yong Park, Yeung-Chul Mun, Young Rok Do, Hun-Mo Ryoo, Je-Jung Lee, Jae Hoon Lee, Won Seog Kim, Cheolwon Suh; Cancer Res Treat. 2015;47(2):173-181. Published online October 28, 2014; DOI: https://doi.org/10.4143/crt.2014.055

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Purpose
This study was conducted to evaluate outcomes in adult patients with Burkitt lymphoma (BL) or Burkitt-like lymphoma treated with an rituximab plus hyper-CVAD (R-hyper-CVAD) regimen by focusing on tolerability and actual delivered relative dose intensity (RDI).
Materials and Methods
Patients ≥ 20 years of age and pathologically diagnosed with BL or Burkitt-like lymphoma were treated with at least one cycle of R-hyper-CVAD as the first-line treatment in this study. Eligible patients’ case report forms were requested from their physicians to obtain clinical and laboratory data for this retrospective study.
Results
Forty-three patients (median age, 51 years) from 14 medical centers in Korea were analyzed, none of which were infected with human immunodeficiency virus. The majority of patients had advanced diseases, and 24 patients achieved a complete response (75.0%). After a median follow-up period of 20.0 months, 2-year event-free and overall survival rates were 70.9% and 81.4%, respectively. Eleven patients (25.6%) were unable to complete the R-hyper-CVAD regimen, including six patients due to early death. The RDIs of adriamycin, vincristine, methotrexate, and cytarabine were between 60% and 65%, which means less than 25% of patients received greater than 80% of the planned dose of each drug. Poor performance status was related to the lower RDIs of doxorubicin and methotrexate.
Conclusion
R-hyper-CVAD showed excellent treatment outcomes in patients who were suitable for dose-intense chemotherapy. However, management of patients who are intolerant to a dose-intense regimen remains problematic due to the frequent occurrence of treatmentrelated complications.

Citations

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Comparison of chemotherapy regimens plus rituximab in adult Burkitt lymphoma: A single-arm meta-analysis
Xiaoxuan Lu, Yu Liu, Ruyu Liu, Jiaxin Liu, Xiaojing Yan, Liren Qian
Frontiers in Oncology.2022;[Epub] CrossRef
Trends in survival of patients with stage I/II Burkitt lymphoma in the United States: A SEER database analysis
Ze‐Long Liu, Pan‐Pan Liu, Xi‐Wen Bi, De‐Xin Lei, Yu Wang, Zhi‐Ming Li, Wen‐Qi Jiang, Yi Xia
Cancer Medicine.2019; 8(3): 874. CrossRef
ERK-dependent IL-6 positive feedback loop mediates resistance against a combined treatment using danusertib and BKM120 in Burkitt lymphoma cell lines
Jun Liu, Junshik Hong, Kwang-Sung Ahn, Junhyeok Go, Heejoo Han, Jihyun Park, Dongchan Kim, Hyejoo Park, Youngil Koh, Dong-Yeop Shin, Sung-Soo Yoon
Leukemia & Lymphoma.2019; 60(10): 2532. CrossRef
Lymphoma epidemiology in Korea and the real clinical field including the Consortium for Improving Survival of Lymphoma (CISL) trial
Kwai Han Yoo, Hyewon Lee, Cheolwon Suh
International Journal of Hematology.2018; 107(4): 395. CrossRef
Recent advances in treating extra-ocular lymphomas
Lauge Hjorth Mikkelsen, Natacha Storm Würtz, Steffen Heegaard
Expert Review of Ophthalmology.2018; 13(4): 205. CrossRef
The Consortium for Improving Survival of Lymphoma (CISL): recent achievements and future perspective
Cheolwon Suh, Byeong-Bae Park, Won Seog Kim
Blood Research.2017; 52(1): 3. CrossRef
Primary lymphomas in the gastrointestinal tract
Jiang Chen Peng, Lu Zhong, Zhi Hua Ran
Journal of Digestive Diseases.2015; 16(4): 169. CrossRef

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The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: Taek-Keun Nam, Jae-Sook Ahn, Yoo-Duk Choi, Jae-Uk Jeong, Yong-Hyeob Kim, Mee Sun Yoon, Ju-Young Song, Sung-Ja Ahn, Woong-Ki Chung; Cancer Res Treat. 2014;46(1):33-40. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.33

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PURPOSE
To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications.
MATERIALS AND METHODS
Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received radiotherapy alone. Ten patients received chemotherapy before radiotherapy, and three patients underwent surgery followed by chemotherapy and radiotherapy. One patient received surgery followed by radiotherapy. All patients received radiotherapy of median dose of 30.6 Gy.
RESULTS
The duration of follow-up ranged from 6 to 158 months (median, 48 months). Five-year overall survival and cause-specific survival rates were 90.3% and 100%. All patients treated with radiotherapy alone achieved pathologic complete remission (pCR) in 31 of the low-grade and in three of the mixed-grade patients. All patients treated with chemotherapy and/or surgery prior to radiotherapy achieved pCR except one patient who received chemotherapy before radiotherapy. During the follow-up period, three patients developed diffuse large B-cell lymphoma in the stomach, and one developed gastric adenocarcinoma after radiotherapy. No grade 3 or higher acute or late complications developed. One patient, who initially exhibited gastroptosis, developed mild atrophy of left kidney.
CONCLUSION
These findings indicate that a modest dose of radiotherapy alone can achieve a high cure rate for low-grade and even mixed-grade gastric MALT lymphoma without serious toxicity. Patients should be carefully observed after radiotherapy to screen for secondary malignancies.

Citations

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Proportion and Characteristics of Helicobacter Pylori-Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Systematic Review and Meta-Analysis
Xiu-He Lv, Qing Lu, Jia-Huan Liu, Bi-Han Xia, Zi-Jing Wang, Zhu Wang, Jin-Lin Yang
Clinical and Translational Gastroenterology.2025; 16(4): e00781. CrossRef
Clinical Management of Patients with Gastric MALT Lymphoma: A Gastroenterologist’s Point of View
Tamara Matysiak-Budnik, Kateryna Priadko, Céline Bossard, Nicolas Chapelle, Agnès Ruskoné-Fourmestraux
Cancers.2023; 15(15): 3811. CrossRef
Magnetic Resonance Imaging-Guided Radiation Therapy for Early-Stage Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Neris Dincer, Gamze Ugurluer, Gorkem Gungor, Teuta Zoto Mustafayev, Banu Atalar, Enis Ozyar
Cureus.2022;[Epub] CrossRef
Development and Validation of a Prognostic Nomogram for Gastric Marginal Zone Lymphoma: a Surveillance, Epidemiology and End Results-based population Study
Mingliang Wang, Cheng Wu, Yida Lu, Xin Xu, Huizhen Wang, Youliang Wu, Xiaodong Wang, Yongxiang Li
Future Oncology.2021; 17(5): 529. CrossRef
Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma
Laurent Quéro, Mouna Labidi, Marc Bollet, Côme Bommier, Sophie Guillerm, Christophe Hennequin, Catherine Thieblemont
World Journal of Gastrointestinal Oncology.2021; 13(10): 1453. CrossRef
Second Cancers in a Patient with Gastric MALT Lymphoma
Lucy Navsaria, Alfonso Badillo, Michael Wang
Case Reports in Medicine.2020; 2020: 1. CrossRef
The Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma using Radiotherapy
Aswin Nagarajan, Arun Sakthivelu, Alexander John, Ramya Ravichandar
Indian Journal of Medical and Paediatric Oncology.2020; 41(04): 559. CrossRef
Favorable radiation field decrease in gastric marginal zone lymphoma
Gabriele Reinartz, Regina P. Pyra, Georg Lenz, Rüdiger Liersch, Georg Stüben, Oliver Micke, Kay Willborn, Clemens F. Hess, Andreas Probst, Rainer Fietkau, Ralf Jany, Jürgen Schultze, Christian Rübe, Carsten Hirt, Wolfgang Fischbach, Martin Bentz, Severin
Strahlentherapie und Onkologie.2019; 195(6): 544. CrossRef
Long-term course of precancerous lesions arising in patients with gastric MALT lymphoma
Anne-Laure Rentien, Michaël Lévy, Christiane Copie-Bergman, Charlotte Gagniere, Jehan Dupuis, Yann Le Baleur, Karim Belhadj, Iradj Sobhani, Corinne Haioun, Jean-Charles Delchier, Aurelien Amiot
Digestive and Liver Disease.2018; 50(2): 181. CrossRef
Gastrointestinal lymphomas: French Intergroup clinical practice recommendations for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFH)
Tamara Matysiak-Budnik, Bettina Fabiani, Christophe Hennequin, Catherine Thieblemont, Georgia Malamut, Guillaume Cadiot, Olivier Bouché, Agnès Ruskoné-Fourmestraux
Digestive and Liver Disease.2018; 50(2): 124. CrossRef
Place de la radiothérapie pour les lymphomes du mucosa-associated lymphoid tissue gastriques : résultats d’une étude rétrospective
L. Ghorbal, A. Hdiji, H. Ben Salah, F. Elloumi, M. Frikha, M. Elloumi, J. Daoud
Cancer/Radiothérapie.2018; 22(8): 763. CrossRef
Les lymphomes gastro-intestinaux
P. Jamet, T. Matysiak-Budnik, L. Brichet, A. Ruskoné-Fourmestraux
Oncologie.2018; 20(5-6): 107. CrossRef
Radiotherapy for localized gastric mucosa–associated lymphoid tissue lymphoma: long-term outcomes over 10 years
Yu Ohkubo, Yoshihiro Saito, Hiroki Ushijima, Masahiro Onishi, Tomoko Kazumoto, Jun-ichi Saitoh, Nobuko Kubota, Hirofumi Kobayashi, Nobuo Maseki, Yu Nishimura, Masafumi Kurosumi
Journal of Radiation Research.2017; 58(4): 537. CrossRef
Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens
L. Gastaud, B. Rossignol, F. Peyrade, D. Ré, J. Thariat, A. Thyss, J. Doyen
Cancer/Radiothérapie.2016; 20(3): 236. CrossRef
Differential somatostatin and CXCR4 chemokine receptor expression in MALT-type lymphoma of gastric and extragastric origin
Susann Stollberg, Daniel Kämmerer, Elisa Neubauer, Stefan Schulz, Ingrid Simonitsch-Klupp, Barbara Kiesewetter, Markus Raderer, Amelie Lupp
Journal of Cancer Research and Clinical Oncology.2016; 142(11): 2239. CrossRef
Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications
Hyeon Woo Lim, Tae Hyun Kim, Il Ju Choi, Chan Gyoo Kim, Jong Yeul Lee, Soo Jeong Cho, Hyeon Seok Eom, Sung Ho Moon, Dae Yong Kim
Radiation Oncology Journal.2016; 34(3): 193. CrossRef
Refractory peptic ulceration following radiation therapy in primary gastric lymphoma: A report of two cases
CHUNYAN ZENG, SHIWEN LUO, NONGHUA LV, YOUXIANG CHEN
Oncology Letters.2015; 9(1): 63. CrossRef
Exclusive moderate-dose radiotherapy in gastric marginal zone B-cell MALT lymphoma: Results of a prospective study with a long term follow-up
Agnès Ruskoné-Fourmestraux, Tamara Matysiak-Budnik, Bettina Fabiani, Pascale Cervera, Hedia Brixi, Karine Le Malicot, Isabelle Nion-Larmurier, Jean-Fançois Fléjou, Christophe Hennequin, Laurent Quéro
Radiotherapy and Oncology.2015; 117(1): 178. CrossRef

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Coexisting with Clonal Evolution and BCR-ABL Mutant in CML Patients Treated with Second-generation Tyrosine Kinase Inhibitors Predict the Discrepancy of in vitro Drug Sensitivity: Jae-Sook Ahn, Yeo-Kyeoung Kim, Se Ryeon Lee, Li Yu, Deok-Hwan Yang, Sang-Hee Cho, Hyun Jeong Shim, Woo Kyun Bae, Je-Jung Lee, Ik-Joo Chung, Myung Gun Shin, Hyeoung-Joon Kim; Cancer Res Treat. 2010;42(1):37-41. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.37

Abstract PDF PubReader ePub

Purpose

Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs.

Materials and Methods

We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months.

Results

Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI.

Conclusion

Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.

Citations

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T315I – a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia
Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 412. CrossRef
Impacto de la mutación T315I en el pronóstico de la leucemia mieloide crónica
Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 418. CrossRef
BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase
T P Hughes, G Saglio, A Quintás-Cardama, M J Mauro, D-W Kim, J H Lipton, M B Bradley-Garelik, J Ukropec, A Hochhaus
Leukemia.2015; 29(9): 1832. CrossRef

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The Efficacy of an Induction Chemotherapy Combination with Docetaxel, Cisplatin, and 5-FU Followed by Concurrent Chemoradiotherapy in Advanced Head and Neck Cancer: Jae-Sook Ahn, Sang-Hee Cho, Ok-Ki Kim, Joon-Kyoo Lee, Deok-Hwan Yang, Yeo-Kyeoung Kim, Je-Jung Lee, Sang-Chul Lim, Hyeoung-Joon Kim, Woong-Ki Chung, Ik-Joo Chung; Cancer Res Treat. 2007;39(3):93-98. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.93

Abstract PDF PubReader ePub

Purpose

This study was performed to determine the feasibility and safety of the use of induction chemotherapy combined with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiation therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN).

Materials and Methods

The patients, that were initially not treated for locally advanced SCCHN, underwent three cycles of induction chemotherapy every 3 weeks at a dose of 70 mg/m² docetaxel D1, 75 mg/m² cisplatin D1, 1000 mg/m² 5-FU D1-4, and subsequently received concurrent chemoradiation therapy.

Results

Forty-nine patients were enrolled in this study and forty-three of the patients completed the treatment. The median duration of follow-up was 18 months (range, 6~39 months). All of the patients had stage III (26.5%) or IV (73.5%) squamous cell carcinoma. After sequential therapy, a complete response and partial response was seen in 28 (65.2%) and 13 (30.2%) patients, respectively. The overall response rate was 95.4%. Overall survival and progression-free survival (PFS) at 2 years were 88.7% and 69.7%, respectively. Grade 3~4 neutropenia occurred in 42.2% of the patients and grade 4 thrombocytopenia in 1 cycle (0.7%). Two patients (4.1%) died during the induction chemotherapy due to pneumonia and a subdural hemorrhage, respectively. The group of patients over 65 years of age showed a significant lower dose intensity than that of patients under 65 years of age, but PFS was not significantly different between two groups (p=0.105).

Conclusion

TPF induction chemotherapy followed by concurrent chemoradiotherapy showed a high level of CR and moderate treatment-induced toxicity. Adequate dose modification in elderly patients should be considered to maintain efficacy and avoid treatment-related toxicity.

Citations

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