About Prof. Chen Saijuan
Prof. Chen Saijuan is a world-renowned haematologist at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and a member of the Chinese Academy of Sciences. She specialises in the molecular diagnosis and targeted treatment of leukaemia and myelodysplastic syndromes. Her team identified the variant chromosomal translocation t(11;17) in APL, cloned the PLZF gene, and elucidated the molecular mechanism by which arsenic trioxide degrades the PML-RARα oncofusion protein. She co-developed the ATRA and arsenic trioxide combination regimen — the Shanghai Protocol — that transformed APL from one of the most rapidly fatal haematological malignancies into the first acute myeloid leukaemia subtype that is essentially curable, with five-year disease-free survival exceeding 90%.
Case Overview
Ms. Guo (pseudonym), a 31-year-old woman, presented with a four-day history of spontaneous bruising, bleeding gums, petechiae, and profound fatigue. Full blood count revealed WBC 28 × 10⁹/L with 72% abnormal promyelocytes, haemoglobin 78 g/L, and platelets 18 × 10⁹/L. Coagulation studies confirmed disseminated intravascular coagulation (DIC). Bone marrow biopsy confirmed APL (FAB M3); FISH and RT-PCR confirmed the PML-RARα fusion transcript. ATRA was commenced immediately; arsenic trioxide was added once DIC stabilised, completing the Shanghai Protocol induction. Day 28 bone marrow confirmed complete haematological remission; quantitative PCR confirmed complete molecular remission — undetectable PML-RARα transcript. She completed consolidation therapy and has remained in molecular remission at three-year follow-up. Ms. Guo reflected: "I was told in the emergency room that I had leukaemia and that it was serious. Prof. Chen's team explained exactly what it was, exactly how they were going to treat it, and exactly what to expect. Four months later I was in remission. Three years later I am well. I owe them everything."
Diagnostic Workup
Peripheral blood film identified hypergranular promyelocytes with Auer rods, triggering immediate haematological assessment. Coagulation profile confirmed DIC, establishing the urgency of treatment initiation. Bone marrow aspirate and trephine biopsy confirmed hypercellular marrow with greater than 80% abnormal promyelocytes (APL, FAB M3). FISH and RT-PCR confirmed the PML-RARα fusion transcript and established the baseline quantitative PCR level for molecular response monitoring. Cytogenetics confirmed t(15;17)(q22;q12). Immunophenotyping confirmed the characteristic APL surface marker profile. Risk stratification classified Ms. Guo as intermediate risk, informing the consolidation strategy.
Prof. Chen's assessment at diagnosis: APL is a haematological emergency — the coagulopathy can be fatal within hours if ATRA is not started immediately. The molecular diagnosis confirms PML-RARα, which means this patient will respond to the Shanghai Protocol. The goal from this moment is complete molecular remission: undetectable PML-RARα transcript by quantitative PCR. That is the standard that gives this patient a greater than 90% probability of long-term cure.
Treatment Strategy and Course
Diagnosis: Acute Promyelocytic Leukaemia (APL, FAB M3) with PML-RARα Fusion, Presenting with Disseminated Intravascular Coagulation — 31-year-old patient, intermediate risk.
Treatment principle: the Shanghai Protocol — ATRA and arsenic trioxide combination targeted therapy, exploiting differentiation induction (ATRA) and PML-RARα oncofusion protein degradation (arsenic trioxide) to achieve complete molecular remission without conventional cytotoxic chemotherapy.
- Emergency stabilisation: ATRA commenced immediately on clinical suspicion; FFP, cryoprecipitate, and platelet transfusion for DIC; DIC resolved within 72 hours of ATRA initiation
- Induction — ATRA + arsenic trioxide (Days 1–28): ATRA 25 mg/m²/day orally; arsenic trioxide 0.16 mg/kg/day IV added Day 4 post-DIC stabilisation; no differentiation syndrome; Day 28: complete haematological remission confirmed
- Molecular remission: Quantitative RT-PCR at end of induction: PML-RARα undetectable — complete molecular remission confirmed on two consecutive samples
- Consolidation (Months 2–4): Four cycles of ATRA and arsenic trioxide per Shanghai Protocol; PML-RARα remained undetectable throughout; treatment completed at month four
- Surveillance: Quantitative PCR every three months for two years, then every six months; bone marrow at 12 months; three-year follow-up: molecular remission maintained, full haematological recovery
Prof. Chen's clinical reflection: Ms. Guo's outcome — complete molecular remission after induction, sustained at three years — is what the Shanghai Protocol was designed to achieve. ATRA forces the leukaemic promyelocytes to differentiate into normal cells; arsenic trioxide degrades the PML-RARα protein that drives the disease. Together, they eliminate the leukaemic clone without the toxicity of conventional chemotherapy. The five-year disease-free survival of greater than 90% is the result of understanding the disease at the molecular level and designing treatment that addresses that molecular target precisely.
Expert Commentary — Prof. Chen Saijuan
1. The Shanghai Protocol: How Molecular Understanding Transformed APL from Fatal to Curable
Before the 1980s, APL was the most rapidly fatal subtype of acute myeloid leukaemia, with median survival measured in days to weeks. The transformation into the first essentially curable AML rests entirely on molecular understanding. Prof. Wang Zhenyi's discovery that ATRA could induce differentiation of APL promyelocytes was the first breakthrough. The identification of PML-RARα as the molecular driver, the discovery that arsenic trioxide degrades this protein, and the elucidation of the molecular mechanism by Prof. Chen Saijuan's team provided the foundation for the combination regimen. The Shanghai Protocol achieves five-year disease-free survival exceeding 90% in standard-risk APL and has been adopted by haematology centres worldwide — the paradigmatic example of molecularly targeted cancer therapy achieving cure rates that conventional chemotherapy could never approach.
2. The Molecular Mechanism of Arsenic Trioxide: From Traditional Medicine to Precision Oncology
Arsenic trioxide was identified as effective in relapsed and refractory APL through clinical observation at Harbin Medical University in the 1990s. Prof. Chen Saijuan's team elucidated the mechanism: arsenic trioxide directly binds to the PML component of PML-RARα, inducing sumoylation and proteasomal degradation. Loss of PML-RARα removes the block on myeloid differentiation and triggers apoptosis of the leukaemic clone. The combination of ATRA (degrading PML-RARα through the retinoic acid receptor pathway) and arsenic trioxide (degrading it through the PML-dependent pathway) produces synergistic elimination of the oncofusion protein — the molecular basis for the superior efficacy of the combination over either agent alone.
3. Molecular Monitoring in APL: Quantitative PCR in Defining Remission and Predicting Relapse
Haematological remission is an insufficient endpoint in APL: patients who achieve morphological remission but retain detectable PML-RARα transcript are at high risk of relapse. Complete molecular remission — undetectable PML-RARα by sensitive quantitative PCR — is the treatment target that correlates with long-term cure. Serial molecular monitoring during and after consolidation enables early detection of molecular relapse before haematological relapse, allowing pre-emptive treatment intensification when disease burden is lowest and the probability of achieving a second molecular remission is highest. Integration of molecular monitoring into the Shanghai Protocol is a key reason for its exceptional long-term outcomes.
How CMCS Shanghai Coordinated This Case
CMCS Shanghai supported Ms. Guo and her family throughout the emergency admission, treatment, and follow-up pathway at Ruijin Hospital, including: emergency consultation coordination with Prof. Chen Saijuan's haematology team from the time of the initial APL diagnosis; bilingual interpretation across all haematology consultations, treatment planning, and follow-up appointments; bilingual explanation of the APL diagnosis, molecular findings, Shanghai Protocol, and molecular remission targets; coordination of bone marrow biopsy, FISH, RT-PCR, cytogenetics, and flow cytometry with bilingual results communication; bilingual consent for induction and consolidation; inpatient coordination during the acute admission; bilingual communication of molecular remission confirmation; and long-term quantitative PCR surveillance scheduling.
For international patients facing a diagnosis of acute leukaemia or other haematological malignancy, Prof. Chen Saijuan's team at Ruijin Hospital offers access to one of the world's most experienced haematology programmes — the centre that developed the Shanghai Protocol. CMCS ensures that expertise is accessible — in the patient's language, with every step coordinated and communicated clearly.
This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.
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