Paroxysmal nocturnal hemoglobinuria induced by the occurrence of BCR-ABL in a PIGA mutant hematopoietic progenitor cell

Tominaga, Ryo; Katagiri, Takamasa; Kataoka, Keisuke; Wee, Rachel; Maeda, Akio; Gomyo, Hiroshi; Mizuno, Ishikazu; Murayama, Tohru; Ogawa, Seishi; Nakao, Shinji

doi:10.1038/leu.2015.268

Cited by 22 publications

(16 citation statements)

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“…Also, one MPN sample out of a few cases tested PNH+ in our series. Despites PNH testing for MPN patients is currently not recommended, several cases have been recently described in which JAK‐2 , and CALR mutations, as well as BCR‐ABL gene rearrangements have been associated with PNH‐positivity , the precise frequency of PNH+ cases among MPN patients deserving further investigations. In contrast to what is described above for AA and MDS cases, presence of hemolysis or cytopenias does not appear to be sufficient indication for PNH testing in patients diagnosed of hematological and/or immunological disorder other than AA, MDS, and MPN, such as leukemia/lymphoma or autoimmune diseases .…”

Section: Discussionmentioning

confidence: 99%

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

Morado

Sandes

Colado

et al. 2016

Cytometry Part B Clinical

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Section: Discussionmentioning

confidence: 99%

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

Morado

Sandes

Colado

et al. 2016

Cytometry Part B Clinical

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“…Variious plausible secondary driver alterations have been reported in occasional cases and implicated in the clonal outgrowth of PIGA-mutated clones, including those affecting HMGA2, NRAS, JAK2, TET2, U2AF1, and even BCR/ABL. 78,[81][82][83][84] However, thus far, no consistently recurrent mutational targets have been identified, even with WES, 78 precluding the indispensable role of these secondary mutations in the development of PNH.…”

Section: Immune Escape As the Mechanism For Chmentioning

confidence: 99%

Clonal hematopoiesis in acquired aplastic anemia

Ogawa

2016

Blood

162

130

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Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolution. Genetic abnormalities are found in ∼50% of patients with AA and, except for PIGA mutations and copy-neutral loss-of-heterozygosity, or uniparental disomy (UPD) in 6p (6pUPD), are most frequently represented by mutations involving genes commonly mutated in myeloid malignancies, including DNMT3A, ASXL1, and BCOR/BCORL1. Mutations exhibit distinct chronological profiles and clinical impacts. BCOR/BCORL1 and PIGA mutations tend to disappear or show stable clone size and predict a better response to IST and a significantly better clinical outcome compared with mutations in DNMT3A, ASXL1, and other genes, which are likely to increase their clone size, are associated with a faster progression to MDS/AML, and predict an unfavorable survival. High frequency of 6pUPD and overrepresentation of PIGA and BCOR/BCORL1 mutations are unique to AA, suggesting the role of autoimmunity in clonal selection. By contrast, DNMT3A and ASXL1 mutations, also commonly seen in CH in the general population, indicate a close link to CH in the aged bone marrow, in terms of the mechanism for selection. Detection and close monitoring of somatic mutations/evolution may help with prediction and diagnosis of clonal evolution of MDS/AML and better management of patients with AA.

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“…Significant advances have been reported in the detection of the GPI‐AP‐deficient cells, as well as in the pathophysiology of the disease. In treatment aspect, recombinant human anti‐complement C5 monoclonal antibodies, new complement inhibitors, and allogeneic hematopoietic stem cell transplantation have made great progress in the field of PNH therapy . China as a developing country, eculizumab is not yet available in China, and we have no experience with eculizumab, so the traditional treatment of PNH is aimed at protecting PNH clone, reducing complement attack and destruction, and alleviating hemolysis.…”

Section: Introductionmentioning

confidence: 99%

Analysis of clinical characteristics of 92 patients with paroxysmal nocturnal hemoglobinuria: A single institution experience in China

et al. 2019

Clinical Laboratory Analysis

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Objectives We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of Chinese paroxysmal nocturnal hemoglobinuria (PNH) patients, and assessed the efficacy and safety of glucocorticoid in PNH patients. Methods The clinical data of 92 PNH cases in our hospital were analyzed, including clinical manifestation, laboratory examination, treatment efficacy, and survival. Results The main clinical manifestations of these patients included hemoglobinuria, anemia, fatigue, dyspnea, headache, abdominal pain, and erectile dysfunction. Glucocorticoid is still the first‐line treatment for PNH patients to control hemolytic attack, and the short‐term remission rate (12 months) is 79.01% (64/81). Meanwhile, the overall survival (OS) of 10 years after diagnosis was estimated as 70.77% (46/65). Moreover, Cox proportional risk model for multivariate analysis showed that the increase in LDH multiple, thrombosis complications, and complicated with bone marrow failure were the independent adverse prognostic factors affecting the survival of PNH patients. Conclusion Paroxysmal nocturnal hemoglobinuria patients in mainland China have various clinical features, while lower incidences of thrombosis and renal damage. Thrombosis and bone marrow failure are two complications with worse prognosis.

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Paroxysmal nocturnal hemoglobinuria induced by the occurrence of BCR-ABL in a PIGA mutant hematopoietic progenitor cell

Cited by 22 publications

References 14 publications

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

Clonal hematopoiesis in acquired aplastic anemia

Analysis of clinical characteristics of 92 patients with paroxysmal nocturnal hemoglobinuria: A single institution experience in China

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