Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonal karyotype, clinical and blast cell features were established in 113 adults, aged 15-68 (mean 31.2) years with acute lymphoblastic leukemia (ALL). The karyotypes were: Philadelphia positive (Ph+), 23 cases; t(4;11), six cases; other chromosome findings (group II), 84 cases. Ph+ patients were older (mean 39.7 years) at presentation than the group II patients (mean 28.3 years) (p less than 0.0001). Ph+ was less frequent than expected in teenagers (15-20 years) (10.3%) and patients aged 21-50 years (21.8%), and more frequent in patients over 50 years old (43.8%) (p less than 0.01). Follow-up (between 0.5 and 4.5 years) was obtained for 108 patients. Age and karyotype (Ph+ versus group II) were prognostically significant for event-free (EFS) and overall survival (S) (p less than 0.001 in each instance). Ph+ patients fared worse than group II cases in all age groups, but karyotype added prognostic significance to age only when Ph+ and t(4;11) cases were combined (group I) (group I versus group II: EFS, p = 0.054; S, p = 0.043). The Ph breakpoint location M-bcr+ (nine cases) and M-bcr- (14 cases) was irrelevant to age (mean 37.7 and 41.3, respectively) and to prognosis. The findings indicate a fundamental difference between the genetics of ALL in most older and the majority of younger patients which may partly explain the increasingly poor prognosis with age.
Leukemia 1991 Mar
PMID:Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. 201 79

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.
 ...
PMID:Molecular insights into the Philadelphia translocation. 205 Jun

Using the polymerase chain reaction and Southern blot analysis the expression was detected of a bcr-abl mRNA lacking abl exon a2. This was due to a corresponding unusual localization of the breakpoint in the c-abl gene and was seen in a patient with Philadelphia (Ph) chromosome positive chronic myelogeneous leukemia in chronic phase. This type of mRNA has been described only once before in two Ph-positive acute lymphoblastic leukemia patients, by Soekarman et al. (1). The abl exon a2 sequences, which are missing in the three reported patients, code for a part of the SH3 region of the abl protein, which is supposed to be involved in negative regulation of the kinase domain. The clinical significance of this finding is discussed.
Leukemia 1991 Jun
PMID:bcr-abl mRNA lacking abl exon a2 detected by polymerase chain reaction in a chronic myelogeneous leukemia patient. 793 77

The CML-specific Philadelphia (Ph1) chromosome is relatively common cytogenetic abnormality of ALL, which has been shown 20% of adult ALL and 5% of child ALL. We analysed here the 12 patients of Ph1-positive ALL, aged 35 to 69-years old, who were experienced in our hospital for latest eight years. In comparison with Ph1-negative ALL, these 12 patients were elder and showed high peripheral and bone marrow leukemic cell counts. Of these, seven patients had 100% Ph1 abnormality in the bone marrow and another five patients showed mosaic marrow patterns of Ph1 and normal chromosomes. Remissioned eight cases had no more Ph1 abnormalities in their bone marrows. Our Ph1-positive ALL revealed B-cell lineage leukemia, since their surface phenotype were Ia+ and CD10+ and they have rearranged immunoglobulin JH genes. Four out of these nine patients had such gene rearrangement in the 5.8kb bcr (major BCR: M-BCR) as CML's patient had. Eight out of twelve Ph1-positive ALL patients (66.7%) achieved complete remission, but the prognosis was so bad since they had shorter remission duration (median 6.7 mos) and survival months (median 11.9 mos) than those of Ph1-negatives.
 ...
PMID:[Philadelphia chromosome-positive adult acute lymphocytic leukemia]. 206 78

The characteristic genetic exchange in chronic myeloid leukemia (CML) is the fusion of the ABL proto-oncogene and a specific part of the BCR or phl gene. Detection of this exchange by cytogenetic or Southern blot analysis is highly diagnostic for CML. The latter approach has not previously been used to quantify the relative proportions of leukemic and non-leukemic cells. We have assessed the feasibility of estimating the relative proportion of leukemic cells present in a sample by densitometric analysis of autoradiographs of Southern blots. In dilution experiments of CML cells with normal cells, a linear relationship could be demonstrated between the relative intensity of the autoradiograph band corresponding bcr rearrangement and the proportion of leukemic cells present. This relationship was found to be largely independent of autoradiograph exposure time. Six patients receiving various therapies have been evaluated for as long as 4.5 years by repeated densitometric and cytogenetic analysis. In general, a declining proportion of Philadelphia (Ph) chromosome positive cells was paralleled by decreasing intensity of the autoradiograph band representing bcr rearrangement. Densitometric changes were often seen prior to the detection of Ph negative cells. This analysis appears to provide a sensitive method for monitoring patients with CML.
Leukemia 1991 Jul
PMID:Densitometric analysis of Southern blot autoradiographs and its application to monitoring patients with chronic myeloid leukemia. 207 39

A 66-year-old woman with acute monoblastic leukemia with t(11;22)(q23;q11), which was subsequently transformed into myeloblastic leukemia is reported. Such karyotype abnormality has not been reported in acute monoblastic leukemia. Cytogenetic analysis revealed 47,XX,+8,t(11;22)(q23;q11) in 19 out of 20 metaphases and 46,XX,del(7)(q22-q36),t(11;22)(q23;q11) in the remaining metaphase. Variant Ph1 was ruled out due to the absence of chimeric bcr-alb mRNAs. In remission cytogenetic findings showed normal karyotype. After 4 months, the patient relapsed with 20% myeloblasts replacing monoblasts in bone marrow. Cytogenetic analysis revealed 46,XX,del(7)(q22-q36),t(11;22)(q23;q11) in all metaphases. A possible explanation for this lineage switch may be the involvement of myelomonocytic progenitor cells.
 ...
PMID:Translocation t(11;22)(q23;q11) in an adult with acute monoblastic leukemia. 208 78

The Philadelphia (Ph) chromosome translocation, t(9:22) (q34;q11) is found in some acute lymphoid leukaemias (ALL) and acute myeloid leukaemias (AML). Although cytogenetically all pH chromosomes appear similar, the 22q11 breakpoints found in acute leukaemias are of two kinds, those within the major breakpoint cluster region (Mbcr-1) of the BCR gene as found in chronic myelogenous leukaemia (CML), and those within the first intron of this gene. In the former group the molecular events are the same as those found in CML, p210 bcr-abl, encoded by 8.5 kb mRNA; however, a new aberrant protein, p190 bcr-abl, is found in the latter group. Ph translocation is also found in a few cases with malignant lymphoma, but it has not been characterized at the molecular level. We describe here a non-Hodgkin's lymphoma case with primary splenic presentation, which showed a complex Ph translocation. Neoplastic cells were of a B-cell origin (HLA-DR+, sIgM+, sIg lambda +, CALLA-). Molecular studies revealed the expression of p190 bcr-abl with no Mbcr-1 rearrangement. Our case indicates that the same Ph translocation as seen in acute leukaemias can be found in haematologic disorders other than leukaemias, suggesting that a c-abl gene activating mechanism may be involved in the pathogenesis of wide spectrum of haematologic malignancies.
 ...
PMID:Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein. 209 24

A permanent cell line, LEF1, has been established from the cells of an adult suffering from a Philadelphia positive acute lymphoblastic leukemia. The LEF1 cell line was obtained by maintaining peripheral blood cells from the patient in culture on a fibroblast feeder; subsequently, an autonomously growing cell population, independent of that feeder layer, developed. The karyotype of the cell line, 46, t(9;22)(q34;q11), was different from the karyotype at diagnosis which had 53 chromosomes and two Philadelphia chromosomes. Furthermore, compared with the initial leukemic blasts, the immortalized cell had three differences in surface phenotype (CD23+, CD11b-, CD10-). However, molecular studies indicated that the breakpoint in the 3' part of the first intron of the BCR gene was unchanged, confirming the leukemic origin of LEF1. The cell line was shown to be Epstein-Barr virus negative.
Leukemia 1990 May
PMID:A new Ph1+, bcr cell line derived from a patient with ALL-L1 gained autonomy in culture concomitant to CD23 expression. 214 94

We studied the cells from three selected patients with Ph-chromosome-negative chronic myeloid leukemia (CML) by Southern blotting, polymerase chain reaction, and in situ hybridization of informative probes to metaphase chromosomes. All three patients had rearrangement of M-BCR sequences in the BCR gene and expression of one or other of the mRNA species characteristic of Ph-positive CML. Leukemic metaphases studied after trypsin-Giemsa banding were indistinguishable from normal. The ABL probe localized both to chromosome 9 and 22 in each case. A probe containing 3' M-BCR sequences localized only to chromosome 22, and not to chromosome 9 as would be expected in Ph-positive CML. Two new probes that recognize different polymorphic regions distal to the ABL gene on chromosome 9 in normal subjects localized exclusively to chromosome 9 in two patients and to both chromosomes 9 and 22 in one patient. These results show that Ph-negative CML with BCR rearrangement is associated with insertion of a variable quantity of chromosome 9 derived material into chromosome 22q11; there is no evidence for reciprocal translocation of material from chromosome 22 to chromosome 9.
Leukemia 1990 Apr
PMID:Interstitial insertion of varying amounts of ABL-containing genetic material into chromosome 22 in Ph-negative CML. 216 19

The Philadelphia chromosome, widely implicated in human leukaemia, is the result of a reciprocal translocation t(9;22) (q34;q11) in which the abl oncogene located at 9q34 is translocated to chromosome 22q11, where it is fused head-to-tail with 5' exons of the bcr gene. In acute lymphoblastic leukaemia, some patients have a breakpoint within the major breakpoint cluster region of the bcr gene, whereas others have the break within its first intron. This second type of translocation results in the transcription of a 7.0-kilobase chimaeric bcr/abl messenger RNA translated into a bcr/abl fusion protein, p190, which has an abnormal tyrosine kinase activity and is strongly autophosphorylated in vitro. We have generated mice transgenic for a bcr/abl p190 DNA construct and find that progeny are either moribund with, or die of acute leukaemia (myeloid or lymphoid) 10-58 days after birth. This finding is evidence for a causal relationship between the Philadelphia chromosome and human leukaemia.
 ...
PMID:Acute leukaemia in bcr/abl transgenic mice. 217 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>