Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a result of clonal evolution typical cases of one of the myelodysplastic syndromes may develop myeloproliferative features. Similarly, typical cases of one of the myeloproliferative disorders may develop dysplastic features, either as part of the natural history of the disease or as a result of exposure to mutagenic drugs or isotopes. There is also an important group of "overlap syndromes" in which cases, at presentation, have both dysplastic and proliferative features. Chronic myelomonocytic leukaemia and many cases of atypical chronic myeloid leukaemia, juvenile chronic myeloid leukaemia and the childhood monosomy 7 syndrome are "overlap syndromes". In addition, a significant minority of cases which fit the generally agreed criteria for a diagnosis of one of the myelodysplastic syndromes (refractory anaemia, refractory anaemia with ring sideroblasts or refractory anaemia with excess of blasts) also have thrombocytosis, neutrophilia, monocytosis, eosinophilia or basophilia.
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PMID:The relationship between the myelodysplastic syndromes and the myeloproliferative disorders. 1049 67

We encountered a 44-year-old woman with suspected chronic myelocytic leukemia (CML) in the acute phase that was difficult to be differentiate from Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). At disease onset, her bone marrow showed an increase in blasts that were negative for myeloperoxydase (MPO) and Positive for CD10, 19, 34, and HLA.DR. Standard type Ph was detected by chromosome analysis, and both major and minor BCR/ABL m-RNA were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) methods. Neutrophil alkaliphosphatase (NAP) score was normal, and neither eosinophilia nor basophilia was observed in peripheral blood. Under a presumptive diagnosis of Ph-positive ALL (L2), the patient was given AdVP (doxorubicin, vincristine, and prednisolone) therapy followed by a regimen of LMVP (L-asparaginase, mitoxantrone, and VP), and obtained a complete remission 2 months later. At that time, FISH analyses of her bone marrow and blood cells no longer detected bone marrow Ph or BCR/ABL fusion gene. A month later, however, the leukemia relapsed with an increase in MPO-positive blasts in bone marrow, and the patient died soon thereafter. We finally concluded that her leukemia was not Ph-positive ALL, but CML in the acute phase at disease onset.
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PMID:[Blast crisis of chronic myelocytic leukemia that was difficult to differentiate from Ph+ acute lymphoblastic leukemia]. 1062 28

A 40-year-old male patient presented with leukocytosis and mild splenomegaly. Bone marrow aspirate showed myeloid hyperplasia and eosinophilia resembling chronic myelogenous leukemia in the chronic phase. Cytogenetic examination of bone marrow cells revealed an unusual karyotype, t(8;13)(p11;q12), in 20/20 metaphases. Not the BCR/ABL, but the ZNF198/FGFR1 chimeric mRNA was detected by reverse transcription-polymerase chain reaction. Since 1992, 12 patients with a similar atypical myeloproliferative disorder with T-cell non-Hodgkin's lymphoma or eosinophilia, associated with a t(8;13) translocation in both bone marrow and lymph node specimens, have been described. The present case is an additional one that should be classified into this new clinicopathologic entity.
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PMID:A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): a Japanese case. 1064 54

The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.
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PMID:Identification of four new translocations involving FGFR1 in myeloid disorders. 1155 Feb 83

Chromosomal aberrations have been reported in most malignant hematopoietic disorders such as acute or chronic myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndromes. Eosinophilic leukemia is a rare hematologic malignancy difficult to distinguish from other forms of idiopathic hypereosinophilic syndrome, so that the diagnosis is often made by exclusion, unless cytogenetic abnormalities can be demonstrated in bone marrow cells. We describe a patient with eosinophilic leukemia whose cytogenetic study shows a t(2;5)(p23;q31). Initial data could suggest a clonal eosinophilia, with an hepatosplenomegaly, severe pancytopenia, and a high level of blood and medullar eosinophilia.
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PMID:Eosinophilic leukemia associated with t(2;5)(p23;q31). 1194 46

Chronic myelocytic leukemia (CML) is a chronic myeloproliferative disorder characterized by cytogenetic or molecular evidence of Philadelphia (Ph) chromosome, t(9;22)(q34;q11). Mild to moderate eosinophilia is commonly seen in CML. However, eosinophilia as a dominant feature of CML is extremely rare. We describe a case of Ph(-) CML with eosinophilia. Loeffler endocarditis, and t(9;12)(q34;p13) that resulted in an ETV6-ABL gene rearrangement/fusion identified to the best of our knowledge, for the first time by using commercially available fluorescence in situ hybridization probes.
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PMID:Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature. 1250 59

We report a case of BCR-ABL-negative atypical chronic myeloid leukemia (CML) with translocation t(4;22) (q12;q11.2) juxtaposing the breakpoint cluster region (BCR) and platelet-derived growth factor receptor-alpha (PDGFRA) genes. The patient was a 57-year-old man with a history of stage IV diffuse large B-cell lymphoma, status post-6 cycles of combination chemotherapy in 1999, who presented in August 2002 with enlarged lymph nodes, anemia, and marked leukocytosis (50 x 10(9) g/dL) consistent with a myeloproliferative disorder (MPD). A bone marrow biopsy showed granulocytic hyperplasia, neutrophilia, and mild eosinophilia. Initial cytogenetic evaluation by interphase FISH for BCR-ABL, to rule out a translocation 9;22, showed a variant signal pattern consistent with rearrangement of BCR at 22q11.2, but not ABL at 9q34. Analysis of the patient's cDNA by polymerase chain reaction (PCR) for BCR-ABL was negative. Cytogenetic analysis showed an abnormal karyotype with rearrangement of chromosomes 4 and 22. PCR amplification and subsequent sequence analysis demonstrated an in-frame 5'-BCR/3'-PDGFRA fusion in the patient's cDNA. PDGFRA encodes a receptor tyrosine kinase and shares structural and organizational homology with the KIT and CSf1R receptor genes. However, although the incidence of MPD involving translocations of PDGFRB has been well established, to our knowledge there are only two previous reports describing a BCR-PDGFRA fusion gene, in 3 patients diagnosed with atypical CML. Here, we report the molecular and cytogenetic characterization of a patient with BCR-PDGFRA-positive MPD who had a complete hematologic response after treatment with imatinib mesylate.
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PMID:Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia. 1503 67

Imatinib mesylate is a small molecule drug that in vitro inhibits the Abelson (Abl), Arg (abl-related gene), stem cell factor receptor (Kit), and platelet-derived growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases. The drug has acquired therapeutic relevance because of similar inhibitory activity against certain activating mutations of these molecular targets. The archetypical disease in this regard is chronic myeloid leukemia, where abl is constitutively activated by fusion with the bcr gene (bcr/abl). Similarly, the drug has now been shown to display equally impressive therapeutic activity in eosinophilia-associated chronic myeloproliferative disorders that are characterized by activating mutations of either the PDGFRB or the PDGFRA gene. The former usually results from translocations involving chromosome 5q31-33, and the latter usually results from an interstitial deletion involving chromosome 4q12 (FIP1L1-PDGFRA). In contrast, imatinib is ineffective, in vitro and in vivo, against the mastocytosis-associated c-kit D816V mutation. However, wild-type and other c-kit mutations might be vulnerable to the drug, as has been the case in gastrointestinal stomal cell tumors. Imatinib is considered investigational for the treatment of hematologic malignancies without a defined molecular drug target, such as polycythemia vera, myelofibrosis with myeloid metaplasia, and acute myeloid leukemia.
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PMID:Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders. 1516 33

Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders characterized by peripheral blood and tissue eosinophilia leading to end-organ damage. Hypereosinophilic syndrome can be fatal, particularly in patients with endomyocardial fibrosis, and treatment has traditionally been palliative or preventive. The disease shares features with myeloproliferative disorders, such as chronic myeloid leukemia, including responsiveness to hydroxyurea and interferon. The tyrosine kinase inhibitor imatinib, a highly effective treatment for chronic myeloid leukemia, has shown efficacy in normalizing eosinophil counts and resolving signs and symptoms in some HES patients. Fusion of the Fip1-like 1 gene (FIP1L1) and the platelet-derived growth factor receptor alpha gene (PDGFRA) was discovered in the majority of patients with imatinib-sensitive HES, and all patients with the fusion responded to imatinib. The product of this fusion gene, FIP1L1-PDGFRalpha, is a constitutively active protein-tyrosine kinase capable of transforming hematopoietic cells. The efficacy of relatively low imatinib concentrations in HES, mediated by inhibition of FIP1L1-PDGFRalpha kinase activity, causally implicates FIP1L1-PDGFRA in the pathogenesis in certain HES patients.
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PMID:Platelet-derived growth factor receptor inhibition to treat idiopathic hypereosinophilic syndrome. 1517 99

We describe a patient with eosinophilic folliculitis (EF) that developed 3 months after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia. Skin biopsy specimen revealed numerous eosinophil infiltrations from the hair follicles to the sebaceous glands. No sign of skin graft-versus-host disease (GVHD) was found. The skin lesions and peripheral eosinophilia subsided within 5 weeks. In the following 8 months, the rash did not recur and GVHD has not developed. Taken together with previous reports, the present case demonstrates that it is important to recognize this distinct skin condition to avoid an inference that it may manifest itself as one of the signs of skin GVHD.
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PMID:Eosinophilic folliculitis in a patient after allogeneic bone marrow transplantation: case report and review of the literature. 1522 72


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