Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BCR”

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 559 records · Page 31Linked to original sources
PubMed1997

Philadelphia-like translocation t(9;22)(q34;q11) found in a follicular lymphoma involving not BCR and ABL but IGL-mediated rearrangement of an unknown gene on 9q34.

In a case of follicular center cell lymphoma (FCCL) without evidence of histologic progression towards a high-grade lymphoma, t(9;22)(q34;q11) was found simultaneously with a t(14;18)(q32;q21) and a t(8;14)(q24;q32). Molecular studies of this case showed BCL2 and MYC rearrangements in addition to the rearrangements of immunoglobulin heavy (IGH) and lambda (IGL) loci. Investigation of the t(9;22) using Southern blot and RT-PCR analysis failed to detect M-bcr or m-bcr rearrangements of BCR. Two-color fluorescence in situ hybridization (FISH) with ABL and BCR probes revealed presence of a "fusion" signal, but its atypical localization [der(9)] and gene order [cen-ABL-BCR-tel] indicated that this translocation differed from the t(9;22) in chronic myeloid leukemia and did not involve either ABL or BCR. In addition, further FISH analysis using 9q34- and 22q11-specific probes localized the breakpoint on chromosome 9 distal to the NOTCH1 gene and the breakpoint on 22q11 in the IGL gene cluster. These results indicate an IGL-mediated rearrangement of an unknown gene at 9q34 that together with BCL2 and MYC might be involved in the lymphomagenesis of the present case of FCCL and perhaps in other cases of non-Hodgkin lymphoma in which t(9;22) is sporadically occurring.

Blotting, Southern↗
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↗
PubMed1988

Linear order of the four BCR-related loci in 22q11.

It has recently been shown the a probe for the 3' end of the BCR gene recognizes a family of four BCR-like genes that map to 22q11. Using a panel of somatic cell hybrids with rearrangement of chromosome 22, we have determined their order within 22q11: BCR-2, BCR4, BCR1, BCR-3, with BCR-2 the most centromere proximal. All of the BCR-like genes map proximal to the 22q11-q12 breakpoint of a t(11;22) in a Ewing sarcoma.

Blotting, Southern↗
PubMed2002

BCR mediated signal transduction in immature and mature B cells.

Ligation of B cell receptors (BCR) on immature B cells may induce apoptosis, while in mature B cells it stimulates cell activation and growth. The signaling pathway regulating the differential functional response, death or survival of the B cell is not fully characterized. We have tested the intracellular signaling requirement of these processes using B cells isolated from the spleen of irradiated auto-reconstituted (transitional immature B cells) and untreated mice (mature B cells), respectively. We compared the BCR induced intracellular [Ca2+] transient, protein tyrosine phosphorylation and ERK phosphorylation, furthermore, the activation of Elk-1 and CREB transcription factors. The BCR induced rise of intracellular [Ca2+] did not significantly differ in the two populations, only a slight difference in the late phase of the response was observed. Immature B cells responded with a maximum tyrosine phosphorylation to a five times lower dose of anti-IgM compared to the mature population. Most importantly, we have found a significant difference in the tyrosine phosphorylation of the Gab family adaptor proteins, Gab1/2. In contrast to mature B cells, crosslinking of BCR on immature B cells did not induce tyrosine phosphorylation of Gab2, thus the Gab2-organized signal amplification complex could not be produced. Furthermore, we detected a significant difference in the kinetics of BCR induced ERK, Elk-1 and CREB phosphorylation. In immature B cells, ERK was transiently phosphorylated, ceasing after 120 min, while in mature cells, ERK phosphorylation was sustained. Elk-1 and CREB activation was also transient in immature B cells, followed the kinetics of ERK phosphorylation. The lack of sustained Erk1/2 activation suppresses the transcription factors necessary for the proliferation signal. Since ERK is regulated by the phosphorylated Gab1/2, these data demonstrate that BCR triggered phosphorylation and signal amplification of Gab1/2 is a critical step in a life or death decision of B cells.

Adaptor Proteins, Signal Transducing↗
PubMed2003

The p54 cleaved form of the tyrosine kinase Lyn generated by caspases during BCR-induced cell death in B lymphoma acts as a negative regulator of apoptosis.

Engagement of the B cell receptor antigen (BCR) triggers apoptosis on immature B cell lines. We report here that BCR triggering leads to caspase activation followed by Lyn cleavage and induction of apoptosis. The cleavage process is mitochondrion-dependent and involves caspases 9 and 7. Stable expression of the cleaved form of Lyn (Lyn-Delta-N) in Ramos B cells impairs BCR-mediated apoptosis as judged by loss of Delta(psi)m, caspase activation and PARP cleavage. Activation of the main survival pathways upon BCR-triggering was unaltered in both cell variants. However, the PI3-K inhibitor Ly294002 resensitizes Lyn-Delta-N cells to apoptosis. Selected cDNA expression arrays revealed that anti-IgM modulates the expression of approximately 20 genes in both cell variants. Among them, only c-Myc was found to be differentially regulated, which suggests a role for c-Myc in the B cell apoptotic response. Interestingly, c-Myc expression decreased more rapidly in Lyn-Delta-N compared with Lyn-WT cells during the first hours of anti-IgM stimulation. Nevertheless, rapid down-regulation of c-Myc following BCR engagement seems to correlate with the resistance of B cells to apoptosis. Thus, the soluble form of Lyn generated by caspases following BCR triggering acts as an inhibitor of B lymphocyte death likely through the modulation of c-Myc expression.

Apoptosis↗
PubMed2003

Bcl-(xL) antagonism of BCR-coupled mitochondrial phospholipase A(2) signaling correlates with protection from apoptosis in WEHI-231 B cells.

Crosslinking of the antigen receptors on the immature B-cell lymphoma, WEHI-231, leads to growth arrest and apoptosis. Commitment to such B-cell receptor (BCR)-mediated apoptosis correlates with mitochondrial phospholipase A2 activation, disruption of mitochondrial function, and cathepsin B activation. CD40 signaling has been reported to rescue WEHI-231 B cells from BCR-driven apoptosis primarily via up-regulation of the antiapoptotic protein Bcl-xL. Coupling of the BCR to the mitochondrial phospholipase A2-dependent apoptotic pathway can be prevented by rescue signals via CD40. We now show that overexpression of Bcl-xL can prevent mitochondrial phospholipase A2 activation, disruption of mitochondrial potential, and postmitochondrial execution of BCR-mediated apoptosis via cathepsin B activation. Moreover, overexpression of Bcl-xL protects WEHI-231 B cells from mitochondrial disruption and apoptosis resulting from culture with exogenous arachidonic acid, the product of phospholipase A2 action, suggesting that Bcl-xL may act to antagonize arachidonic acid-mediated disruption of mitochondrial integrity. However, although Bcl-xL expression can mimic CD40-mediated rescue of BCR-driven apoptosis, it cannot substitute for CD40 signaling in the reversal of BCR-mediated growth arrest of WEHI-231 B cells. Rather, CD40 signaling additionally induces conversion of arachidonic acid to prostaglandin E2 (PGE2), which promotes WEHI-231 B-cell proliferation by restoring the sustained, cycling extracellular signal-regulated/mitogen-activated protein kinase (ErkMAPkinase) signaling required for cell cycle progression.

Animals↗
PubMed2006

CD72 down-modulates BCR-induced signal transduction and diminishes survival in primary mature B lymphocytes.

CD72, a 45-kDa type II transmembrane glycoprotein carrying an ITIM motif, is believed to be an inhibitory coreceptor of the BCR. Mature B cells lacking CD72 show enhanced Ca(2+) mobilization and are hyperproliferative in response to BCR ligation. However, the signal transduction pathways downstream of BCR signaling that transmit the inhibitory effect of CD72 in mature B cells remain unknown. To address this question, we used hen egg lysozyme-specific BCR transgenic mice to elucidate the differential cell signaling between wild-type and CD72-deficient B cells in response to hen egg lysozyme Ag stimulation. Our results demonstrate that CD72 predominantly down-regulates the major signal transduction pathways downstream of the BCR, including NF-AT, NF-kappaB, ERK, JNK, p38-MAPK, and PI3K/Akt in mature B cells. CD72 ligation with anti-CD72 Ab (K10.6), which mimics the binding of CD100 (a natural ligand for CD72) to release the inhibitory function of CD72, augments cell proliferation, Ca(2+) flux, IkappaBalpha activation, and ERK MAPK activity upon Ag stimulation in wild-type B cells. In addition, we show direct evidence that CD72 promotes cell cycle arrest and apoptosis after Ag stimulation in mature B cells. Taken together, our findings conclude that CD72 plays a dominant role as a negative regulator of BCR signaling in primary mature B lymphocytes.

Animals↗
PubMed2005

Regulation of tyrosine phosphorylation during the CD40-mediated rescue of Ramos-BL B cells from BCR-triggered apoptosis.

The regulation of tyrosine phosphorylation is essential for BCR-triggered cellular responses during the selection process in the germinal centres. We were interested in examining the temporal regulation of tyrosine phosphorylation following CD40 cross-linking of anti-IgM-triggered Ramos-BL B cells. CD40 co-stimulation of anti-IgM-treated Ramos-BL B cells rescued them from growth inhibition and apoptosis, even when anti-CD40 Abs were added up to 12 h after the cross-linking of the BCR. The initial up-regulation of tyrosine phosphorylation triggered by BCR cross-linking is followed by tyrosine dephosphorylation after 12 h of stimulation, coinciding with pro-caspase-3 processing and PARP cleavage. We find that CD40 co-stimulation rescues BCR-triggered Ramos-BL B cells only before the irreversible inhibition of tyrosine kinase activity after 12 h of BCR cross-linking and that this is coupled with up-regulation of tyrosine phosphorylation; thus demonstrating the importance of the late regulation of tyrosine phosphorylation for CD40-mediated rescue of Ramos-BL B cells from BCR-triggered G1 growth arrest and apoptosis.

Apoptosis↗
PubMed1988

Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X-linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.

Blast Crisis↗
PubMed1988

Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia.

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.

Alleles↗
PubMed1988

Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3' bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.

Blast Crisis↗
PubMed1994

Simultaneous expression of RBTN-2 and BCR-ABL oncogenes in a T-ALL with a t(11;14)(p13;q11) and a late-appearing Philadelphia chromosome.

Cytogenetic analysis of a pediatric patient with T-cell acute lymphoblastic leukemia (T-ALL) revealed a mosaic karyotype, 47,XX,+17,t(11;14)(p13;q11)/47,XX,+17,t(9;22)(q34;q11),t(11;14) (p13;q11). DNA blot analysis was used to examine the break-point within the BCR gene on chromosome 22 and showed that the breakpoint occurred within the 20-kb minor breakpoint cluster region (m-bcr) located within the first intron of the BCR gene. Immunoprecipitation analysis demonstrated that the leukemic cells expressed the P185 BCR-ABL protein tyrosine kinase. P185 BCR-ABL has previously been shown to be expressed in most cases of Ph+ acute leukemia of myeloid and B-progenitor origin. Here, we demonstrate for the first time that P185 can also be expressed in the T-cell lineage. DNA blot hybridization was also used to characterize the t(11;14) translocation. This showed rearrangement on chromosome 11 within the T-ALLbcr region, upstream of the RBTN-2 gene. Polymerase chain reaction revealed the presence of RBTN-2 transcripts in the leukemic cells. Finally, comparison of the T-ALLbcr, BCR-ABL, IGH, TCR beta and gamma gene rearrangements in leukemic cells obtained at the time of diagnosis and at first relapse showed that relapse occurred in a leukemic clone indistinguishable from the major Ph+ clone involved at diagnosis. Together, these data support a multistep pathogenesis in which the Philadelphia (Ph) chromosome translocation appeared subsequent to the +17 and t(11;14) and imparted a growth advantage over the Ph-negative cells that carried these abnormalities.

Base Sequence↗
PubMed2002

Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukemia in Taiwan.

From 1986 to 1998, 26 (23%) of 114 adult acute lymphoblastic leukemia (ALL) patients and 11 (4%) of 328 pediatric patients were found to have Philadelphia (Ph) chromosome. In the 30 patients with available data at diagnosis, 18 (60%) had extra-chromosomal abnormalities. They included 1q duplication (5/18, 28%), supernumerary Ph chromosome (4/18, 22%), 9p abnormalities (3/18, 17%), 7q deletion/monosomy 7 (3/18, 17%), trisomy 19 (1/18, 6%), and trisomy 8 (1/18, 6%). Excluding those with specific cytogenetic changes, only one patient had hyperdiploid karyotype with more than 50 chromosomes. The incidence of 1q duplication was higher and that of hyperdiploidy was lower in this study than has been previously reported. There was no prognostic implication of these additional cytogenetic abnormalities. With fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR), 14 (27%) of 53 unselected adult ALL patients and 2 (5%) of 38 unselected pediatric patients were BCR-ABL-positive, including one adult and two children without Ph chromosome. The BCR-ABL fusion genes/transcripts were also present in all other 16 selected Ph-positive ALL patients. The BCR-ABL fusion subtypes were determined in all these 32 patients: 91% (11/12) childhood cases showed m-type fusion gene while 45% (9/20) adult ones did so (P = 0.0083). The clinical outcome was similar between the two groups of patients with m-type and M-type BCR-ABL. In conclusion, both cytogenetic and molecular studies are very helpful for identifying the subgroup of ALL patients with Ph/BCR-ABL. The additional cytogenetic abnormalities and subtypes of BCR-ABL fusion genes/transcripts had no significant implications in this group of patients.

Actins↗
PubMed2005

Overproduction of BCR-ABL induces apoptosis in imatinib mesylate-resistant cell lines.

BACKGROUND: Imatinib mesylate, a BCR-ABL tyrosine kinase inhibitor, induces apoptosis in chronic myeloid leukemia cells. Resistance to imatinib is currently the most important concern of this treatment. One of the main mechanisms of this resistance is overexpression of BCR-ABL. METHODS: In the current study, the authors investigated the correlation between BCR-ABL overexpression and apoptosis in BaF/BCR-ABL and LAMA84 cell lines resistant to imatinib suddenly deprived of the inhibitor, and compared with their sensitive counterpart. RESULTS: Removal of imatinib from culture medium led to a decrease in Bcr-Abl protein expression by Day 5, which was sustained for > or = 3 weeks of imatinib deprivation. Apoptosis was observed after 3 days of imatinib deprivation in resistant lines accompanied by caspase activation, loss of membrane asymmetry (annexin V staining), and alteration of mitochondrial potential (dihexyloxacarbocyanine iodide [DiOC6]). Transient activation of the STAT5/Bcl-xL pathway and Akt kinase activity preceded these responses. CONCLUSIONS: Thus, imatinib removal led to apoptosis of BCR-ABL-overexpressing leukemic cells, a phenomenon that could be exploited to sensitize imatinib-resistant cells to the cytotoxic effect of other drugs.

Antineoplastic Agents↗
PubMed1994

CGG-repeat polymorphism of the BCR gene rules out predisposing alleles leading to the Philadelphia chromosome.

The Philadelphia chromosome (Ph) is associated with leukemia, most frequently of the chronic myelogenous variety. The Ph chromosome is a translocation chromosome which gains oncogenic potential through the fusion of the ABL oncogene of chromosome 9 with the BCR gene of chromosome 22. The Ph is believed to arise from random chromosome rearrangement with a subsequent selective advantage of the malignant cell line. However, alleles may be present in the population which predispose toward this specific rearrangement. We used a highly polymorphic CGG-repeat polymorphism within the first exon of the BCR gene to determine BCR allele frequencies among 26 leukemia patients with the Ph chromosome and 63 control individuals. Eight BCR alleles of variable CGG-repeat length were present in both groups at statistically similar frequencies and in Hardy-Weinberg equilibrium. We therefore concluded that there are no alleles of the BCR gene that have a major predisposing influence on the development of the Ph chromosome and subsequent leukemia.

Alleles↗
PubMed2006

Gene therapy for BCR-ABL+ human CML with dual phosphorylation resistant p27Kip1 and stable RNA interference using an EBV vector.

BACKGROUND: BCR-ABL-mediated chronic myelogenous leukemia (CML) CD34(+) cell proliferation mostly depends on the nucleo-cytoplasmic ratio of the cyclin-dependent kinase inhibitor p27. The ubiquitin-ligase SCF(Skp2) promotes degradation of phosphorylated p27 at T187 in the nucleus, resulting in G1/S progression of the cells. On the other hand, phosphatidylinositol-3-kinase (PI3K)-directed T157 nuclear localization signal (NLS) phosphorylation results in cytoplasmic sequestration of p27, leading to abnormal integrin-mediated proliferation of CD34(+) CML cells. METHODS: We demonstrate the generation of an engineered Epstein-Barr virus (EBV) vector with a BAC backbone that has the unique capacity to carry doubly modified (DM) p27 (i.e. T187A, T157A p27) along with the BCR-ABL siRNA expression construct. The HSV-tk suicide gene has also been incorporated in the same vector, which promotes apoptosis in a BCR-ABL-independent pathway. RESULTS: Expression of DM p27 markedly inhibits proliferation of BCR-ABL(+) primary human CML cells. Moreover, DM p27 strongly inhibits the growth of imatinib-resistant CML cells, compared to the T157A p27 (SM p27). The CML growth inhibition is found to be the result of significant G1/S arrest with concomitant increase in hypophosphorylated retinoblastoma (Rb). Moreover, the EBV vector mediated stable RNA interference induces apoptosis in K562 cells and reduces myeloid colony forming units. CONCLUSIONS: We therefore propose a multi-gene delivery strategy for BCR-ABL(+) CML cells by targeting not only the fusion transcript, but also the downstream signaling, to overcome drug resistance in the acute phase of CML.

Active Transport, Cell Nucleus↗
PubMed2006

Quantification of change in phosphorylation of BCR-ABL kinase and its substrates in response to Imatinib treatment in human chronic myelogenous leukemia cells.

Phosphorylation by the constitutively activated BCR-ABL tyrosine kinase is associated with the pathogenesis of the human chronic myelogenous leukemia (CML). It is difficult to characterize kinase response to stimuli or drug treatment because regulatory phosphorylation events are largely transient changes affecting low abundance proteins. Stable isotope labeling with amino acids in cell culture (SILAC) has emerged as a pivotal technology for quantitative proteomics. By metabolically labeling proteins with light or heavy tyrosine, we are able to quantify the change in phosphorylation of BCR-ABL kinase and its substrates in response to drug treatment in human CML cells. In this study, we observed that BCR-ABL kinase is phosphorylated at tyrosines 393 and 644, and that SH2-domain containing inositol phosphatase (SHIP)-2 and downstream of kinase (Dok)-2 are phosphorylated at tyrosine 1135 and 299, respectively. Based on the relative intensity of isotopic peptide pairs, we demonstrate that the level of phosphorylation of BCR-ABL kinase as well as SHIP-2 and Dok-2 is reduced approximately 90% upon treatment with Imatinib, a specific inhibitor of BCR-ABL kinase. Furthermore, proteins, such as SHIP-1, SH2-containing protein (SHC) and Casitas B-lineage lymphoma proto-oncogene (CBL), are also regulated by Imatinib. These results demonstrate the simplicity and utility of SILAC as a method to quantify dynamic changes in phosphorylation at specific sites in response to stimuli or drug treatment in cell culture.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Investigation of bcr-abl transcription by Ph-positive chronic myeloid leukemia progenitors.

It is now feasible to investigate bcr-abl transcription by the progeny of Ph-positive (Ph+) early and committed hemopoietic progenitor cells from patients with chronic myeloid leukemia (CML). Cells from individual colonies can be bisected and each half analyzed by cytogenetics or the reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect the bcr-abl transcript using internal nested oligonucleotide primers that flank the chimeric gene junction. We previously showed that some Ph+ colonies have undetectable PCR products for bcr-abl. When colonies are generated in the presence of alpha interferon (IFN-alpha) bcr-abl transcripts are undetectable in the majority of Ph+ colonies. These data suggest a potential mechanism for the action of IFN-alpha in Ph+ CML and indicate the need for a combined approach with cytogenetics and RT-PCR in analyzing the bcr-abl gene.

DNA, Neoplasm↗