Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
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PMID:[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. 163 23

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder that is characterized by splenomegaly and marked elevation of the blood leukocyte count with granulocyte in maturity. Ph chromosome was identified in CML in 1960 and was found to clearly result from reciprocal translocation between chromosome 9 and chromosome 22 (t(q;22)) (q34;q11). CML arises from a single pluripotent hematopoietic stem cell with the Ph chromosome and demonstration of the Ph chromosome in blood or marrow cells establishes and unequivocal diagnosis of CML. The Ph chromosome is recognized as the cytogenetic result of a rearrangement of the ABL gene on chromosome 9 and the BCL gene on chromosome 22, which leads to the creation of a BCR/ABL fusion gene on chromosome 22. Abnormal ABL-related protein with increased tyrosine kinase activity suggested a molecular mechanism of CML. The BCR/ABL fusion gene can be found not only in the chromosome but in interphase nuclei by fluorescence in situ hybridization (FISH). We employed both fluorescence activated cell sorter (FACS) and FISH to study the lineage involvement of individual stem cells and progenitor cells in patients with CML. Evidence of BCR/ABL fusion was found in pluripotent stem cells (CD34+, Thy1+), myeloid cells, B progenitor cells (CD34+, CD19+) and T/NK progenitor cells (CD34+, CD7+, CD5+) but not mature T cells (CD3+) or natural killer cells (CD3-, CD56+). These data suggested that BCR/ABL gene fusion occurs in pluripotent stem cells and that Ph+ T cells and natural killer cells are eliminated during differentiation.
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PMID:[Progress in laboratory medicine in chronic myeloid leukemia]. 991 8

This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.
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PMID:Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study. 1124 96

There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.
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PMID:BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). 1206 77

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.
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PMID:Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era. 1996 94

The World Health Organization classifies atypical chronic myeloid leukemia (aCML) as a myeloproliferative/myelodisplastic hematological disorder. The primary manifestations are leukocytosis with disgranulopoiesis, absence of basophilia and/or monocytosis, splenomegaly and absence of Philadelphia chromosome or BCR/ABL fusion. Overall 50-65% of patients demonstrate karyotypic abnormalities, although no specific cytogenetic alterations have been associated with this disease. X chromosome alterations have been rarely reported in myeloid malignancies. Although Isodicentric X, idic(X)(q13) is well known in females with myelodysplastic syndromes (MDS), little data are available on X isochromosome and its pathogenetic potential in these disorders. i(X)(p10) is observed in a variety of hematologic malignancies, both myeloid and lymphoid, as a unique abnormality, as well as part of a more complex karyotype, in females and less frequently in male patients. The present report describes the first patient with aCML, with documented isolated i(X)(p10), who developed a secondary acute myeloid leukemia (sAML).
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PMID:Identification of i(X)(p10) as the sole molecular abnormality in atypical chronic myeloid leukemia evolved into acute myeloid leukemia. 2946 60

Rare chronic myelogenous leukemia (CML) patients manifested as the primary blast phase without a chronic and accelerated phase. The occurrence of a t(8;21) translocation in secondary blast phase of CML or Philadelphia chromosome positive acute myelogenous leukemia (Ph+ AML) has been reported previously. No case of primary blast phase of chronic myelogenous leukemia (CML-BP) bearing one clone with t(9;22) and t(8;21) simultaneously has been reported. One Chinese patient presenting with extensive spontaneous ecchymosis and enlarged spleen diagnosed as acute myelogenous leukemia (AML) by smear and immunophenotype was given chemotherapy including daunorubicin 3 days and cytarabine 7 days without a tyrosine kinase inhibitor (TKI) drug at the beginning. Fresh frozen plasma and 4-factor prothrombin complex concentrate was also transfused for coagulation disorder. However, fusion genes BCR/ABL p210 and AML1/ETO were both positive and karyotype analysis showed the abnormalities of t(9;22) and t(8;21) in the same clones. Bone marrow aspirate on 7th day of chemotherapy indicated hypocellularity with 45% blasts remaining. Cytarabine was prolonged to nine days combined with imatinib 600 mg per day. His bone marrow aspirate after complete remission revealed t(8;21) clones disappearing, especially FISH of bone marrow smear detecting the BCR/ABL fusion signals in the basophilic erythroblasts, which confirmed his diagnosis as primary blast phase of CML rather than Ph+ AML. Thus, we report for the first time one patient diagnosed as primary blast phase of CML presenting with t(9;22) and t(8;21) simultaneously.
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PMID:Co-existence of t(9;22) and t(8;21) in primary blast phase of chronic myelogenous leukemia: clinical experience and literature review. 3193 3