Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Philadelphia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1985

Variant Philadelphia translocation in an immunologically and clinically typical case of chronic myeloid leukaemia.

Cytogenetic analysis of bone marrow from a chronic myeloid leukemia patient in chronic phase revealed a classical Philadelphia chromosome from a complex translocation t(2;9;22). The break points on 9 and 22 were, apparently, the same as for the standard translocation (9;22). However, whereas the terminal band of 9 (9q34) was translocated in the usual site, that is on 22q-, the tract deleted from 22 was present on band p13 of chromosome 2. The finding of this rare 22 translocation in classical CML would seem to support the hypothesis that the crucial event in the pathogenesis of CML is the translocation of band 9q34, that contains the c-abl oncogene, onto the Ph' chromosome, rather than the translocation of the tract deleted from 22 to some other chromosome site.

Aged↗
PubMed1986

Silver-stained nucleolar organizer regions in bone marrow cells and peripheral blood lymphocytes of Philadelphia chromosome-positive chronic myelocytic leukemia patients.

Silver-stained nucleolar organizer regions (Ag-NOR) in bone marrow cells and/or phytohemagglutinin-stimulated peripheral blood lymphocytes were compared between six normal healthy persons as controls and 22 Philadelphia chromosome (Ph)-positive chronic myelocytic leukemia (CML) patients, to examine if any disease associated changes occur in the expression of Ag-NOR. Although the frequency of Ag-NOR-positive cells and the number of Ag-NOR per cell were generally greater in lymphocytes than in bone marrow cells in both controls and CML patients, the Ag-stainability of these cell types in CML patients was considerably heterogeneous, compared with that found in controls. The peripheral lymphocytes of CML patients in the chronic phase, but not in the blastic phase, exhibited a significantly lowered Ag-stainability when compared with those of controls. while no such difference was observed between bone marrow cells of controls and leukemia patients in both phases of CML. In the blastic phase, however, the occurrence of Ag-NOR on the Ph of CML bone marrow cells was significantly less than expected. The present findings are discussed in relation to the existing data on the Ag-NOR expression in both normal and neoplastic cells.

Adolescent↗
PubMed1987

Phenylbutazone-induced myelodysplastic syndrome with Philadelphia translocation.

We present a case of a 69-year-old white male with a 3-year history of a myelodysplastic syndrome probably induced by phenylbutazone, and which developed into an overt leukemic phase. Chromosome analysis in the leukemic phase revealed the bone marrow cells to contain a Philadelphia translocation [46,XY,t(9;22)(q34;q11)]. We discuss the possible association between a prior history of exposure to hemotoxins and myelodysplastic syndromes, and the rarity of a Ph translocation in drug-induced hematologic malignancy.

Aged↗
PubMed1987

Four cases with complex Philadelphia translocations, including one with appearance de novo of a "masked" Ph.

Four cases of chronic myelogenous leukemia (CML) with complex Philadelphia (Ph) translocations are described. The first case was that of a 50-year-old woman in the chronic phase of CML. Her leukemic cells showed a complex Ph translocation involving chromosomes #9, #11, and #22 [i.e., t(9;9;22;11)(11qter----11q11::9q11----9q34:: 9p11----9pter;22qter----22q11::9q34?;11 pter----11q11::22q11----22qter)]. In addition to the complex Ph translocation, the leukemic cells contained del(10)(p13). The second case was that of a 21-year-old man whose leukemic cells contained a translocation involving chromosomes #5, #9, and #22 [i.e., t(5;22;9)(q31;q11;q34)], resulting in a "masked" Ph chromosome. The third case was that of a 37-year-old man whose leukemic cells had a complex Ph translocation involving chromosomes #8, #9, and #22 [i.e., t(8;9;22)(q13;q34;q11)]. The fourth patient was a 41-year-old woman diagnosed as having CML in myeloid blastic phase, at which time the first specimen was examined by us. This blood sample showed a karyotype of 45,XX, -9, -17, -22, +mar1, +mar2,9q+. No Ph chromosome was present. A standard Ph translocation was detected in the cells obtained from the spleen, when the patient underwent splenectomy for treatment of the blastic crisis. Subsequent specimens obtained from the blood and bone marrow showed that the leukemic cells contained three clones: 45,XX, -9, -17, -22, +mar1, +mar2,9q+/46,XX, -17, +mar1,t(9;22)(q34;q11)/46,XX,t(9;22)(q34;q11). Cells with the "masked" Ph chromosome were thought to have been derived from the clone with the standard Ph translocation. We postulate that some variant Ph translocations, including those with a "masked" Ph chromosome, may be generated by a stepwise process following the genesis of a standard Ph translocation.

Adult↗
PubMed1987

Transposition of breakpoint cluster region (3' bcr) in CML cells with variant Philadelphia translocations.

A probe derived from the 3' end of the CML breakpoint cluster region (bcr) was localized in chronic myelocytic leukemia (CML) cases with complex Philadelphia translocations, [t(8;9;22)(q13;q34;q11) and t(12;9;22)(p11;q34;q11)], and with "masked" Ph chromosomes, [t(9;5;22)(q34;q31;q11) and t(9;22)(q22;q34)], by a chromosomal in situ hybridization technique. In some cases, the 3' bcr rearrangements in the DNA were examined with Southern blot analysis. In each case, a significant accumulation of grains hybridized to the 3' bcr probe was observed at chromosomal segments derived from the long arm of a chromosome #22. In some cases, the accumulation of grains was detected on both translocated segments derived from the 22q and terminal portions of Ph chromosomes; Southern blot analysis revealed that breakage in chromosome #22 occurred within DNA sequences of the 3' bcr probe involved in the Ph translocations. In a CML cell line, K562, no accumulation of grains hybridized to the 3' bcr probe was detected, except at 22q11 of the normal chromosomes #22; Southern blot analysis of this cell line revealed that the 3' bcr sequences were missing. Thus, the data presented here suggest a complexity in the formation of "masked" Ph chromosomes.

Chromosome Banding↗
PubMed1987

Breakpoint cluster region rearrangements in chronic myelogenous leukemia with a masked Philadelphia chromosome.

Cytogenetic and molecular analyses were performed in a case of chronic myelogenous leukemia. The cytogenetic study revealed that the leukemic cells of this patient contained a three-way translocation involving chromosomes #5, #9, and #22, resulting in a masked Philadelphia chromosome; the karyotype of the leukemic cells was 46,XY,t(5;22;9)(q31;q11;q34). Southern blot analysis of leukemic cell DNA was performed using a 1.1 kb HindIII-EcoRI breakpoint cluster region (bcr) probe. The results showed that BglII digested DNA showed two abnormal bcr fragments (i.e., 5.2 kb and 2.7 kb) in contrast to the results with DNA from two patients with a standard Ph chromosome [t(9;22)(q34;q11)] who showed one normal 5.0-kb bcr fragment in addition to altered fragments of about 4.3 kb or 4.0 kb. Bam HI digests of DNA from the leukemic cells of the patient with the masked Ph chromosome showed two bands (3.3 kb and 6.5 kb), whereas, DNA from the two patients with standard Ph translocations showed only a 3.3-kb bcr fragment. The results indicate that the molecular events in a masked Ph affect the bcr locus in a manner similar to that seen in standard Ph chromosomes.

Adult↗
PubMed1987

Silver bands in chronic granulocytic leukemia. II. The Philadelphia chromosome.

To test if rRNA gene activity in the Philadelphia (Ph) chromosome nucleolar organizing regions (NOR) differs from other NOR we scored silver banding patterns in leukemic cells of 32 patients (one patient was sampled twice) in the chronic phase of chronic granulocytic leukemia. The average number of bands per NOR in banded cells of these patients was 0.40 +/- 0.06 for the Ph NOR, not significantly different from the 0.41 +/- 0.02 per D chromosome NOR or the 0.41 +/- 0.04 per G. Across the 33 cases, the number of different Ph NOR banded in at least one cell (23 of 33, 70%) was also closely similar to the cumulative maximum number of chromosome D NOR banded per cell (137 of 198 banded, 69%) and G NOR banded (67 of 99, 67%). We conclude that the activity of rRNA genes in Ph NOR is closely similar to that of the other nine NOR in each CGL cell. In situ hybridization of 3H-labeled complementary rRNA to NOR of two patients revealed that the mean number of Ph NOR grains fell within the range of the other NOR. Also, grain distributions across the NOR of leukemic cells closely matched those of stimulated lymphocytes. Thus, a limited sampling has shown no evidence for consistent differences or changes in the rRNA gene number of Ph NOR.

Adult↗
PubMed1987

Cytogenetic and molecular characterization of a masked Philadelphia chromosome in chronic myelocytic leukemia.

A case of typical chronic myeloid leukemia with an apparently Philadelphia-negative karyotype is described. Molecular studies confirmed the cytogenetic interpretation of a standard Ph rearrangement, with secondary involvement of 22q- in a translocation with chromosome #5, leading to its masking. The chromosomal regions engaged in the standard t(9;22) were not modified and the molecular rearrangements of Ph were also conserved. The hematologic and clinical features were apparently not influenced by the events leading to the masking of Ph. Further similar observations with both cytogenetic and molecular characterization are needed to better identify the possible clinical consequences of these complex changes.

Adolescent↗
PubMed1988

Variant Philadelphia translocations in CML: correlation with fragile sites.

Of 175 CML patients studied, 14 variants were found, seven of which are presently described. The breakpoints involved in the translocation, other than 9q34 and 22q11, are 3p21, 5q13, 6p21, 7q22, 10q22, and 11p13. Fragile sites were investigated in some of these patients. In two cases a coincidence between fragile site location and breakpoint of the third chromosome involved in Philadelphia formation was found. This observation suggests that the fragile sites can lead to Ph variants in patients developing CML.

Adult↗
PubMed1988

Molecular and clinical investigations in Philadelphia chromosome-negative chronic myelogenous leukemia.

We performed molecular studies in five cases of Philadelphia (Ph) translocation-negative chronic myelogenous leukemia (CML). Among the five, one case showed a 7q - anomaly; the remaining four had normal karyotypes. The 5' or 3' breakpoint cluster region (bcr) DNA probes detected rearrangements in two of the five cases. The two cases with bcr rearrangement showed clinical and hematologic manifestations similar to those with Ph-positive CML; for example, basophilia in the peripheral blood and marked hepatosplenomegaly. On the other hand, the three Ph-negative CML cases without bcr rearrangement manifested somewhat different clinical manifestation; that is, they did not respond to busulfan therapy in the chronic phase. Our observations suggest a heterogeneity in Ph-negative CML with at least two subtypes: one with a rearranged bcr gene showing clinical and hematologic features akin to those of CML with a Ph translocation, and the other without such a rearrangement and with a somewhat different clinical feature. Furthermore, the present data point to the possibility of the existence of Ph-negative CML without bcr rearrangement.

Adolescent↗
PubMed1988

Historical communication: Philadelphia-positive chronic myelogenous leukemia followed for 27 years.

The patient we studied was diagnosed as having chronic myelogenous leukemia (CML), possibly radiation-induced, in 1960 at age 9, and a Philadelphia chromosome was first demonstrated in the neoplastic cells in 1961. Her subsequent clinical course has been cyclic, requiring periodic therapy, but there has been no karyotypic progression. A study in 1987 continued to show the typical t(9;22) translocation as the only cytogenetic alteration, and concurrent molecular investigation of the neoplastic cells revealed a breakpoint cluster region rearrangement, also typical of CML. The chromosomal and molecular data provide no obvious explanation for her remarkably prolonged survival.

Bone Marrow↗
PubMed1988

Association of the Philadelphia chromosome and 5q- in secondary blood disorder.

A patient developed a secondary blood disorder 7 years after radiotherapy for a gastric lymphoma. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with transient polycythemia, progressive thrombocythemia, and hyperleukocytosis. Chromosome analysis performed in the terminal phase showed del(5)(q13q31),t(9;22)(q34;q11), and a complex rearrangement involving chromosomes #2 and #3. A correlation between chromosomal abnormalities and hematologic findings could be established. In this case, we have assumed that the Philadelphia translocation is a late event, due to prior mutagen exposure, and its association with a common secondary abnormality (5q-), followed by a progressively developing myeloproliferative phase. Furthermore, the association of Ph and 5q- in a single clone seems to indicate that the same stem cell is affected by these two abnormalities.

Anemia, Refractory, with Excess of Blasts↗
PubMed1988

"Masked" Philadelphia chromosome resulting from a t(X;22) in chronic myeloid leukemia.

A rare cytogenetic finding in chronic myeloid leukemia is reported. It consisted in a "masked" Philadelphia chromosome, resulting from an unusual translocation between chromosomes #22 and X. The t(X;22) was present in 100% of direct and cultured bone marrow cell preparations. Chromosome #9 did not seem to be involved in the formation of the Ph marker. Involvement of the X chromosome in karyotypic changes of hematologic diseases, with particular respect to chronic myeloid leukemia, is discussed.

Chromosomes, Human, Pair 22↗
PubMed1988

Myelodysplastic syndrome with Philadelphia-like chromosome without bcr rearrangement.

The case of a 62-year-old Japanese male with a myelodysplastic syndrome and a Philadelphia (Ph)-like chromosome, which probably involved bands 11q23 and 22q11, is presented. Cytogenetic analysis of bone marrow cells revealed a Ph chromosome as well as -5, -7, +8, +11, -16, and an extra Ph. Some of the cells had a normal karyotype. Molecular analysis using breakpoint cluster region probes (5' bcr and 3' bcr) did not detect a rearrangement within the bcr DNA sequences, indicating that the breakpoint at 22q11 occurred outside the bcr. Furthermore, the bone marrow cells from this patient did not express an 8.5-kb c-abl mRNA. Thus, the Ph chromosome in this case differs from that of Ph-positive chronic myelogenous leukemia, and the present case suggests that we should retain the term of "Ph-like chromosome" in such cases.

Anemia, Refractory, with Excess of Blasts↗
PubMed1988

A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia.

Three patients had complex translocations involving 9q34, 22q11, and a third chromosome (Xq11, 7q11.2, or 15q11.2). Two patients had apparently simple variant Philadelphia (Ph) translocations, t(19;22) and t(11;22), with no obvious involvement of chromosome 9, and the Ph was masked in the t(11;22). In situ hybridization studies showed transposition of the abl gene from chromosome 9q34 to the breakpoint cluster region (bcr) of chromosome 22 in all five patients; this was confirmed by rearrangements of the bcr gene in leukemic DNA. In situ hybridization also showed that the bcr-3' and c-sis probes consistently translocated to recipient chromosomes X, 1, 7, 11, and 15, whereas IgC lambda remained on chromosome 22q. These results confirm that association of abl and bcr is a consistent feature of chronic myeloid leukemia irrespective of the cytogenetic presentation and support the conclusion of Hagemeijer that all simple variant Ph translocations are, in fact, complex and involve at least three chromosomes.

Adult↗