Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndr...Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.展开更多
Background The FIP1L1-PDGFRa fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia （CEL） and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate. Meth...Background The FIP1L1-PDGFRa fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia （CEL） and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate. Methods In 24 hypereosinophilic syndromes （HES） patients, using reverse transcriptase-polymerase chain reaction （RT-PCR）, nested PCR and sequence analysis, we investigated the frequency of FIPIL1-PDGFRa and other abnormalities of tyrosine kinase family genes like PDGFRa, PDGFRβ, C-KIT, FGFR1, ABL and FLT3 as well as gene mutation ＂hotspots＂, like MPL515 and JAK2V617F, frequently involved in myeloproliferative diseases. Fluorescence in situ hybridization was used to confirm the 4q 12 deletion. Results The FIP1L1-PDGFRa fusion transcript was found in 8 （33%） of 24 patients with HES, corresponding to the chromosome 4q12 deletion identified by FISH. The FIP1L 1-PDGFRα-associated patients diagnosed with CEL, frequently had hepatosplenomegaly, eosinophil-related tissue damage, anemia, thrombocytopenia, myelofibrosis and a short overall survival time. Nevertheless, imatinib mesylate induced rapid and complete hematological responses in treated FIP1L1-PDGFRa cases, followed by molecular remission and reversal of myelofibrosis. FIP1L1-PDGFRa fusion could co-exist with other mutations of tyrosine kinase family genes, like FLT3 or PDGFRβ. We also demonstrated that the SNPs of PDGFRβ were associated with selective splicing of exon 19 in case 20. Conclusions Correlating the CEL genotype with phenotype, FIP1L1-PDGFRa emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L 1-PDGFFla fusion gene is valid for both CEL diagnosis and therapy surveillance.展开更多
文摘Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.
基金This work was supported, in part, by the Chinese National Key Program for Basic Research （973, No. 2004CB518600）, the Chinese National High Tech Program （863, No. 2006AA02A405 and No. 2006AA02A301）, the National Natural Science Foundation of China （No. 30521003）, the Key Discipline Program of Shanghai Municipal Education Commission （No. Y0201）, the Shanghai Commission of Science and Technology, the Shanghai Rising Star Program （No. 05QMX1429）, the Scientific Research Foundation for the Returned Overseas Chinese Scholars, and by the Samuel Waxman Cancer Research Foundation Laboratory, the Co-PI Program of Shanghai Ruijin Hospital/Shanghai Jiao Tong University School of Medicine.
文摘Background The FIP1L1-PDGFRa fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia （CEL） and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate. Methods In 24 hypereosinophilic syndromes （HES） patients, using reverse transcriptase-polymerase chain reaction （RT-PCR）, nested PCR and sequence analysis, we investigated the frequency of FIPIL1-PDGFRa and other abnormalities of tyrosine kinase family genes like PDGFRa, PDGFRβ, C-KIT, FGFR1, ABL and FLT3 as well as gene mutation ＂hotspots＂, like MPL515 and JAK2V617F, frequently involved in myeloproliferative diseases. Fluorescence in situ hybridization was used to confirm the 4q 12 deletion. Results The FIP1L1-PDGFRa fusion transcript was found in 8 （33%） of 24 patients with HES, corresponding to the chromosome 4q12 deletion identified by FISH. The FIP1L 1-PDGFRα-associated patients diagnosed with CEL, frequently had hepatosplenomegaly, eosinophil-related tissue damage, anemia, thrombocytopenia, myelofibrosis and a short overall survival time. Nevertheless, imatinib mesylate induced rapid and complete hematological responses in treated FIP1L1-PDGFRa cases, followed by molecular remission and reversal of myelofibrosis. FIP1L1-PDGFRa fusion could co-exist with other mutations of tyrosine kinase family genes, like FLT3 or PDGFRβ. We also demonstrated that the SNPs of PDGFRβ were associated with selective splicing of exon 19 in case 20. Conclusions Correlating the CEL genotype with phenotype, FIP1L1-PDGFRa emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L 1-PDGFFla fusion gene is valid for both CEL diagnosis and therapy surveillance.
