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

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
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PMID:Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. 155 89

The clinico-haematological and evolutive features of five patients with Ph'-positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients.
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PMID:[Chronic myeloid leukemia beginning as thrombocythemia. Analysis of 5 cases]. 158 31

Two cases of unclassified chronic myeloproliferative disorders (UCMPD), diagnosed by hematological, cytogenetic and DNA analyses, are described. Case 1: a 63 year old female was admitted because of leukocytosis (96,800/microliters) and splenomegaly. Hematological examinations revealed an increase of the granulocytes in the peripheral blood and bone marrow. The neutrophil alkaline phosphatase (NAP) score was 121. The patient developed blast crisis after 12 months of the chronic phase. Case 2: a 48 year old male was presented with fever and leukocytosis (20,000/microliters). Hematological examinations revealed an increase of granulocytes in the peripheral blood and bone marrow. The NAP score was 33. Maturation-arrest in granulocytic series and morphological abnormalities of marrow cells were not observed in the two cases. Cytogenetic analysis of bone marrow cells disclosed 46, XX, i (17 q) in case 1 and 47, XY, +8 in case 2. Southern blot analysis using 3' bcr probe and TransProbe-1 showed no bcr rearrangement. These cases are thought to be valuable in order to clarify the relationship between UCMPD and CMPD such as Ph1 negative chronic myelocytic leukemia and myelodysplastic syndromes.
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PMID:[Two cases of unclassified chronic myeloproliferative disorders]. 160 19

Therapy with alpha-interferon (IFN alpha) can suppress the Ph1-positive hemopoiesis in a percentage of patients with chronic myelogenous leukemia (CML). We used IFN alpha to treat a 30-year-old CML patient, characterized by favourable prognostic signs (such as low leukocytosis, absence of splenomegaly and no increase in bone marrow blasts) at diagnosis, and obtained a complete remission, as evaluated by Southern blot and cytogenetic analysis, after one year of treatment. However, the polymerase chain reaction (PCR) revealed the persistence of a minimal residual disease. The IFN alpha therapy was stopped and the hematological status remained stable until eighteen months later, when a cytogenetic analysis revealed the appearance of a clone characterized by t(9;22) and trisomy 8, accounting for 30% of bone marrow metaphases. This cell population spontaneously regressed in the following months, before any cytotoxic treatment. However, as leukemic cells, detected by PCR, were still present, the patient received a high dose chemotherapy, which induced the complete eradication of the Ph1-positive clone, as demonstrated by the absence of bcr-abl transcript at the PCR reaction. Molecular and cytogenetic remission persist one year later, without any further therapy.
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PMID:Transient cytogenetic relapse in a Ph1-positive chronic myelogenous leukemia patient previously treated with alpha-interferon. 162 97

A 63 year-old woman was referred to our hospital because of fever and increased number of blasts in the bone marrow. On physical examination she had slight hepatomegaly but no splenomegaly. Laboratory tests disclosed a hemoglobin level of 8.5 g/dl; a WBC count of 13,200/microliter with 26% blasts; a platelet count of 51,000/microliter. A bone marrow aspirate was normocellular with 74% blasts and 37% blasts were stained positive for myeloperoxidase. Cell surface markers for HLA-DR, CD10, CD19, CD13, CD33 were positive. Karyotype analysis revealed 46, XX, t (9q+; 22q-) and 45XX, -7, t (9q+; 22q-). Southern analysis showed rearrangement of immunoglobulin heavy chain but not T cell receptor beta gene. Rearrangements in M-BCR were not detected with 5' or 3' bcr probes. After 2 courses of chemotherapy, blasts decreased to 7% with recovery of normal elements and 11 out of 20 metaphases of the bone marrow cells were normal karyotype. These findings suggest that this case was de novo Ph1 positive acute leukemia which demonstrated both lymphoid and myeloid features.
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PMID:[Biphenotypic acute leukemia with Ph1 chromosome, M-BCR-, myeloperoxidase+, and CALLA+]. 164 7

An autopsy case of polycythemia vera with der(15) and der(20) associated with remarkable neutrophilia was reported. A 87-year-old man was diagnosed as polycythemia vera in August 1987. The red blood cell count was 621 x 10(4)/microliters, Ht 58.5% and the white blood cell count 45,400/microliters with 92% neutrophils. The splenomegaly, increased red blood cell volume and the low erythropoietin level were present. The arterial SaO2 value was above 92%. The chromosome analysis of bone marrow cells revealed 46, XY, -15, -20, +der(15)t(15;?)(q13-15;?), +der(20)t(20;?)(q11;?). The breakpoint in No. 20 was in q11. The remarkable leukocytosis with relative and absolute neutrophilia were observed. Particularly late in the clinical course the white blood cell count was 92,900/microliters with 99% neutrophils. The Ph1 chromosome was negative and the bcr rearrangement was not detected. He died of bronchopneumonia in January 1989. At the autopsy findings neither the marrow fibrosis nor the extramedullary leukemic cell infiltration was noticed.
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PMID:[Polycythemia vera with der(15) and der(20) associated with remarkable neutrophilia]. 177 54

v-abl, the oncogene transduced by Abelson murine leukemia virus, was first characterized by its ability to transform lymphoid cells. bcr-abl, the oncogene formed by a t(9;22) translocation thought to occur in human hematopoietic stem cells, is detectable in almost all cases of chronic myelogenous leukemia (CML), a malignancy of granulocytic cells. bcr-abl also causes a CML-like syndrome in mice whose bone-marrow cells are infected with a retrovirus transducing the gene. More recent reports have suggested that v-abl can, however, cause a disease similar to CML. We demonstrate here that v-abl, when transduced in a helper virus-containing system, causes disease similar to, but distinct from, the CML-like syndrome induced by bcr-abl. Animals whose bone marrow has been infected by v-abl virus develop modest splenomegaly, marked granulocytosis, and malignant disease of several hematopoietic cell types. Unlike animals with CML-like disease resulting from bcr-abl, the polymorphonuclear leukocytes from animals infected with a v-abl construct do not contain the v-abl provirus at a significant frequency. Histopathologic analysis also shows significant differences between the diseases caused by v-abl and bcr-abl.
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PMID:v-abl causes hematopoietic disease distinct from that caused by bcr-abl. 186 78

A 60-year-old woman was admitted because of fatigue. Physical examination revealed prominent peripheral lymphadenopathy, marked tonsillar swelling and hepatosplenomegaly. The leukocyte count was 68,900/microliters with 75% lymphoid blasts and 5% basophils. The karyotype of the blood cells was 46, XX, Ph1/47, XX, Ph1, +Ph1. The diagnosis of CML in blast crisis was made. After chemotherapy using adriamycin, cyclophosphamide, vincristine, and prednisolone (CHOP), lymphadenopathy and splenomegaly reduced and lymphoid blasts disappeared from the blood and bone marrow. At that time only single Ph1 (46, XX, Ph1) clone was detected in her bone marrow. Four months later, hematological relapse accompanied by lymphadenopathy occurred and DNA analysis of the blasts showed the rearrangement of bcr gene. The simultaneous chromosomal analyses of the blood, bone marrow and lymph node revealed that almost all cells examined had the karyotype "47, XX, Ph1, + Ph1". In spite of repeated chemotherapy the patient did not improve and died. This case suggests a relationship between lymphadenopathy and double Ph1 chromosomes in CML.
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PMID:[Prominent lymphadenopathy and double Ph1 chromosomes as initial and recurrent manifestations of chronic myelogenous leukemia in blast crisis: report of a case and review of the literature]. 224 24

The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML.
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PMID:Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. 240 27

A case of well-documented and -illustrated megakaryoblastic transformation is described in a patient with thrombocythemia passing through a stage of myelofibrosis without features of chronic granulocytic leukemia. Immunocytologic studies with the use of conventional and monoclonal antibodies against platelet membrane glycoproteins and electron microscopic investigations, demonstrating bull's-eye granules and platelet peroxidase positivity, proved the megakaryocytic differentiation of the blast cells. From the onset of the disease as well as during the megakaryoblastic transformation, the Philadelphia (Ph1) karyotype, 46XX t(9:22) (q34:q11), was found in peripheral blood and bone marrow cells as the only clonal abnormality. Southern blot analysis of DNA extracted from the blast cells revealed a rearrangement within the bcr on chromosome 22 similar to findings in chronic granulocytic leukemia. The presentation with excessive small and abnormal megakaryocytes in the initial and subsequent bone marrow and the rapid progressive myelofibrosis and splenomegaly differentiate the Ph1 chromosome-positive thrombocythemia from the chronic myeloproliferation of thrombocythemia in its primary form or associated with polycythemia vera.
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PMID:Philadelphia chromosome-positive thrombocythemia and megakaryoblast leukemia. 347 3


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