scholarly journals Detection of derivative 9 deletion by BCR-ABL fluorescence in-situ hybridization signal pattern to evaluate treatment response in CML patients

2009 ◽  
Vol 17 (1-2) ◽  
pp. 13-18
Author(s):  
Beena Patel ◽  
Pina Trivedi ◽  
Manisha Brahmbhatt ◽  
Sarju Gajjar ◽  
Ramesh Iyer ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
Partial Responder ◽  
Signal Pattern ◽  
Fish Signal

Background: To evaluate prognostic effect of submicroscopic deletions involving breakage and fusion points of the derivative chromosome 9 and 22 in chronic myeloid leukemia in untreated patients and their follow up samples to correlate with disease outcome. Methods: The study included 78 pretreatment (PT) samples from CML patients and 90 follow-up samples, classified as complete responders (CR, n=33), nonresponders (NR, n =54), and partial responder (PR, n=3) depending on the treatment status of the follow-up samples. Karyotype analysis was performed on metaphases obtained through short term cultures of bone marrow and blood. Detection of BCR-ABL fusion gene was performed using dual color dual fusion (D-FISH) translocation probes. Results: BCR-ABL fusion gene detection by D-FISH showed ABL-BCR deletion on derivative 9 in 47.8% of nonresponders which was higher as compared to pretreatment (11%). Mix D-FISH signal pattern was found in around 20% of pretreatment and non-responder samples. Average interval from chronic phase to blast crisis and accelerated phase was respectively 3.5 and 18 months and accelerated to blast crisis was 16.5 months from the time of diagnosis. The follow-up duration of 31 patients responded to therapy was significantly higher (p=0.0001) as compared to 45 patients who did not respond to therapy. Variant D-FISH signal pattern was seen at the time of diagnosis in patient who responded to therapy as well as those patients who did not respond to therapy. Conclusion: This is the first study from India reporting deletion in ABL, BCR, or ABL-BCR on derivative 9 did not correlate with response to therapy.

The poor prognostic significance of deletions of derivative chromosome 9 in Chinese patients with chronic myelogenous leukemia

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17535-17535
Author(s):  
J. Li ◽  
W. Xu ◽  
W. Wu ◽  
S. Zhang ◽  
Y. Zhu
Keyword(s):  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Blast Crisis ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chinese Patients ◽  
Striking Difference ◽  
Derivative Chromosome

17535 Background: Chronic myeloid leukemia (CML) is characterized by formation of the BCR/ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Deletions of the derivative 9 chromosome [der(9)] in 10- 15% of CML patients with a standard Ph translocation and in >30% of CML patients with a variant Ph translocation. Subsequent studies demonstrated that CML patients who carry a der(9) deletion progress more rapidly to blast crisis and have a shorter survival than those without a deletion. The characteristics of Chinese patients with each hematologic malignancy compared with those in other countries have not yet been clarified. This prompted us to perform molecular and cytogenetic analyses on Chinese patients with CML. Methods: To study the incidence and the prognostic significance of the derivative chromosome 9 [der(9)] deletions in on Chinese patients with CML, a series of 48 BCR/ABL positive Chinese CML blast crisis (CML-BC) patients were investigated using dual colour dual fusion BCR/ABL probe and fluorescence in situ hybridization (FISH). Results: Eight (16.7%) cases showed der(9) deletions, and the deletions were also existed in chromosome preparations made at diagnosis. The estimated median length of chronic phase for patients with der(9) deletions was 18 months (range 4–38 months) compared to 48 months (range 0–204 months) for patients without deletions. Kaplan-Meier analysis revealed a striking difference in length of chronic phase between with and without der(9) deletions, and this difference was highly significant by log-rank analysis. Der(9) deletions are not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases transformed to acute nonlymphocytic leukemia (ANLL) and those to acute lymphoid leukemia (ALL). Conclusions: The results indicate that FISH technique could effectively detect the der(9) deletions. Der(9) deletions occur at the time of Ph translocation. CML patients with der(9) deletions have more rapid process and poorer prognosis. Deletion status is a powerful prognostic factor for patients with CML. Der(9) deletions might not lead to transformation to specific type in CML. No significant financial relationships to disclose.

Results of Second Generation Tyrosine Kinase Inhibitor Frontline Therapy in Chronic Myeloid Leukemia with Variant Philadelphia Chromosome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3774-3774
Author(s):  
Carlos G. Romo ◽  
Hagop M Kantarjian ◽  
Susan O'Brien ◽  
Alfonso Quintas-Cardama ◽  
Steven M. Kornblau ◽  
...  
Keyword(s):  
Research Funding ◽  
Second Generation ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Initial Therapy ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
Free Survival ◽  
Ph Chromosome

Abstract Abstract 3774 Background: Variant Philadelphia (Ph) chromosomes are observed in 5–10% of patients (pts) with CML, involving one or more additional chromosomes besides 9 and 22. Deletions of derivative chromosome 9 (del der (9)) occur in 10–15% of pts, and frequently these abnormalities coexist. Prior to the advent of TKIs pts with variant Ph or del der (9) had a worse outcome. With imatinib the adverse prognosis conferred by these abnormalities has been minimized. To our knowledge there are no published reports regarding the outcomes of pts with variant Ph or del der(9) while on treatment with a 2nd generation TKI as initial therapy for CML. We analyzed the significance of these abnormalities among patients with CML in chronic phase (CP) enrolled in 2 parallel trials of dasatinib or nilotinib as initial therapy. Patients and Methods: A total of 205 pts with CML in CP treated between 2005 and 2012 at our institution with frontline dasatinib or nilotinib based protocols were included in this analysis. Among them 193 (94%) had classic Ph chromosome, and 12 (6%) had a variant Ph chromosome. Nineteen of the 205 pts (9%) had del der (9). Their characteristics and outcomes were compared. Results: Only one additional chromosome was present in the Ph rearrangement in each of the variant Ph-positive cases. The additional chromosomes found were 17 in three patients and chromosomes 1, 3, 4, 5, 9, 11, 14, 19, 21 in one patient each. Del der (9) was found in 2 of 12 pts with variant Ph and in 17 with classic Ph. Five (50%) of the pts with variant Ph were treated with dasatinib and 5 (50%) with nilotinib. Of those with classical Ph 93 (48%) were treated with dasatinib and 100 (52%) with nilotinib. The median age was 48 yrs (range 17 to 86) for those with classic Ph, and 53 yrs (24 to 79) for those with variant Ph. The Sokal risk group for those with classic Ph was high in 16 (8%), intermediate in 53 (28%), and low in 124 (64%). For the patients with variant Ph risk classification was 10%, 50% and 40%. No significant differences were observed in response to therapy between pts with variant Ph and those with classic Ph (CCyR 100% vs. 93%; MMR 100% vs. 85%, respectively), or between those with del der (9) and those without it (CCyR 100% vs. 93%; MMR 100% vs. 84%). The 3-year probability of overall survival (OS) was 99% for pts with classic Ph and 89% for those with variant Ph. Corresponding values for 3-year event-free survival (EFS) were 96% and 89%, and transformation-free survival (TFS) 99% and 100% respectively. 3-year OS, EFS and TFS were also similar between pts with del derv (9) and those without it (Table 1). Among the 2 pts with concomitant variant Ph and del der (9), one achieved CCyR at 3 months and has maintained it with 12 months of follow up. The second one achieved CCyR but became pregnant during the course of treatment; the TKI was temporarily discontinued and she lost cytogenetic response, but regained response after 3 months of reinitiating TKI therapy and delivering a healthy baby. Conclusion: The presence of variant Ph chromosome or del der (9) does not affect the clinical characteristics or outcome of pts with CML CP treated with second generation TKI as initial therapy. Disclosures: Kantarjian: Pfizer: Research Funding; Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding. Jabbour:Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Cortes:Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding.

scholarly journals Relationship of bcr breakpoint to chronic phase duration, survival, and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase [see comments]

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2035-2041
Author(s):  
SW Morris ◽  
L Daniel ◽  
CM Ahmed ◽  
A Elias ◽  
P Lebowitz
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Chimeric Protein ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Phase Duration ◽  
Total Survival

Strong evidence implicates fusion of control elements and 5′ sequences of the bcr gene of chromosome 22 with 3′ sequences of the c-abl gene of chromosome 9 in the pathogenesis of Ph-positive and certain cases of Ph- negative chronic myelogenous leukemia (CML). Since this fusion gene gives rise to a chimeric tyrosine protein kinase with transforming potential, and since the bcr exon contribution to this chimeric protein is variable, the question has arisen as to whether bcr breakpoint location and bcr exon contribution could influence the clinical course of CML. Prior studies have yielded conflicting results on this point. Here we have looked, in a manner approximating a prospective analysis, at the relation of bcr breakpoint localization to the duration of chronic phase, total survival, and blast crisis phenotype in 81 patients presenting in the chronic phase of CML. We have found no significant differences in chronic phase duration or total survival among patients with breakpoints in the three major subregions of a breakpoint cluster region within the bcr gene. These findings indicate that chronic phase duration and total survival cannot be predicted from bcr breakpoint for CML patients presenting in chronic phase and suggest that unknown oncogenic events determining the onset of blast crisis are the prime determinants of prognosis. Combined analysis of blast crisis cell lineage in our patients and patients presented in a previous study has revealed an overall ratio of myeloid:lymphoid (M:L) crisis of 3.4:1, but a striking predominance of myeloid crisis in patients with breakpoints in subregion 2 (M:L of 9:1), and a lower than expected M:L ratio (1.6:1) among patients with breakpoints in subregion 3 (P for subregion 2 versus 3 = .012; subregions 0,1,2 versus 3 = .012; subregions 0,1,3 versus 2 = .032). The molecular basis for this divergence from the anticipated M:L ratio in patients with breakpoints in bcr subregions 2 and 3 is unknown.

Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2281-2286 ◽  
Author(s):  
Alfonso Quintas-Cardama ◽  
Hagop Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Response Duration ◽  
Cytogenetic Response ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Derivative Chromosome

AbstractDeletions of derivative chromosome 9 [der(9)] can be identified by fluorescence in situ hybridization (FISH) in 10% to 15% of patients with chronic myeloid leukemia (CML). Patients with der(9) deletions have been reported to have an adverse outcome when treated with chemotherapy, interferon, and possibly imatinib mesylate. We investigated the frequency and prognostic significance of der(9) deletions among 352 patients with CML treated with imatinib mesylate at our institution, in whom a deletion status of der(9) was determined. Thirty-three patients (9%; 95% CI 0.07, 0.13) (30 in chronic phase, 3 in accelerated phase) had der(9) deletions. The rates of major (82% vs 79%, P = 0.82) and complete cytogenetic response (76% vs 66%, P = .33) with imatinib mesylate therapy were similar in patients with and without der(9) deletions, respectively. After a median follow-up of 28 months, there was no difference in overall survival (P = .30) or response duration (P = .49) in patients with and without deletions. In a multivariate analysis, der(9) deletions had no significant impact on response, survival, or response duration. We conclude that treatment with imatinib mesylate overcomes the adverse prognostic significance of der(9) deletions in patients with CML.

Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1160-1168 ◽  
Author(s):  
Brian J. P. Huntly ◽  
Anthony Bench ◽  
Anthony R. Green
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Scoring Systems ◽  
Chromosome 9 ◽  
Rapid Progression ◽  
Molecular Heterogeneity ◽  
Derivative Chromosome ◽  
New Paradigm

Abstract Chronic myeloid leukemia (CML) is characterized by formation of a BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Recently the development of new fluorescence insitu hybridization (FISH) techniques has allowed identification of unexpected deletions of the reciprocal translocation product, the derivative chromosome 9, in 10% to 15% of patients with CML. These deletions are large, span the translocation breakpoint, and occur at the same time as the Ph translocation. Such deletions therefore give rise to previously unsuspected molecular heterogeneity from the very beginning of this disease, and there is mounting evidence for similar deletions associated with other translocations. Several studies have demonstrated that CML patients who carry derivative chromosome 9 deletions exhibit a more rapid progression to blast crisis and a shorter survival. Deletion status is independent of, and more powerful than, the Sokal and Hasford/European prognostic scoring systems. The poor prognosis associated with deletions is seen in patients treated with hydroxyurea or interferon, and preliminary evidence suggests that patients with deletions may also have a worse outcome than nondeleted patients following stem cell transplantation or treatment with imatinib. Poor outcome cannot be attributed to loss of the reciprocal ABL-BCR fusion gene expression alone, and is likely to reflect loss of one or more critical genes within the deleted region. The molecular heterogeneity associated with the Philadelphia translocation provides a new paradigm with potential relevance to all malignancies associated with reciprocal chromosomal translocations and/or fusion gene formation.

scholarly journals Relationship of bcr breakpoint to chronic phase duration, survival, and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase [see comments]

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2035-2041 ◽  
Author(s):  
SW Morris ◽  
L Daniel ◽  
CM Ahmed ◽  
A Elias ◽  
P Lebowitz
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Chimeric Protein ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Phase Duration ◽  
Total Survival

Abstract Strong evidence implicates fusion of control elements and 5′ sequences of the bcr gene of chromosome 22 with 3′ sequences of the c-abl gene of chromosome 9 in the pathogenesis of Ph-positive and certain cases of Ph- negative chronic myelogenous leukemia (CML). Since this fusion gene gives rise to a chimeric tyrosine protein kinase with transforming potential, and since the bcr exon contribution to this chimeric protein is variable, the question has arisen as to whether bcr breakpoint location and bcr exon contribution could influence the clinical course of CML. Prior studies have yielded conflicting results on this point. Here we have looked, in a manner approximating a prospective analysis, at the relation of bcr breakpoint localization to the duration of chronic phase, total survival, and blast crisis phenotype in 81 patients presenting in the chronic phase of CML. We have found no significant differences in chronic phase duration or total survival among patients with breakpoints in the three major subregions of a breakpoint cluster region within the bcr gene. These findings indicate that chronic phase duration and total survival cannot be predicted from bcr breakpoint for CML patients presenting in chronic phase and suggest that unknown oncogenic events determining the onset of blast crisis are the prime determinants of prognosis. Combined analysis of blast crisis cell lineage in our patients and patients presented in a previous study has revealed an overall ratio of myeloid:lymphoid (M:L) crisis of 3.4:1, but a striking predominance of myeloid crisis in patients with breakpoints in subregion 2 (M:L of 9:1), and a lower than expected M:L ratio (1.6:1) among patients with breakpoints in subregion 3 (P for subregion 2 versus 3 = .012; subregions 0,1,2 versus 3 = .012; subregions 0,1,3 versus 2 = .032). The molecular basis for this divergence from the anticipated M:L ratio in patients with breakpoints in bcr subregions 2 and 3 is unknown.

scholarly journals CML patients in blast crisis have breakpoints localized to a specific region of the BCR

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 448-455 ◽  
Author(s):  
K Schaefer-Rego ◽  
H Dudek ◽  
D Popenoe ◽  
Z Arlin ◽  
JG Mears ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Large Area ◽  
Translocation Breakpoints ◽  
Ph Chromosome

Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between chromosomes 9 and 22. This activates the abl oncogene by moving it from chromosome 9 and combining it with sequence located on chromosome 22. The new fusion gene, with chromosome 22 sequence at its 5′ end and chromosome 9-abl sequence at its 3′ end, generates a new messenger RNA (mRNA) and protein that are implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 are concentrated within a 6 kilobase (kb) region termed the breakpoint cluster region (bcr). This study was designed to determine whether chronic-phase and blast crisis patients had identifiable differences in the structure of their Ph chromosomes. Restriction mapping of the chromosome 22 translocation breakpoints performed for 26 patients showed that the breakpoints of eight of the nine patients in blast crisis were in the 3′ portion of the bcr, whereas the breakpoints in the 17 patients in the chronic phase were clustered in the 5′ portion of the bcr. This suggests a strong correlation between a 3′ bcr breakpoint and blast crisis in CML.

Imatinib Therapy for Chronic Myeloid Leukemia: An Experience From Eastern India.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4498-4498
Author(s):  
Swati Dasgupta ◽  
Ujjal Ray ◽  
Soma Mukhopadhyay ◽  
Chinmoy Kumar Bose ◽  
Sanjoy Sarkar ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Imatinib Therapy ◽  
Haematological Parameters ◽  
Hematological Parameter

Abstract Abstract 4498 Background: Chronic Myeloid Leukemia(CML) is an myloproliferative disorder characterized by the expansion of clone of hematopoietic cells that carries the Philadelphia chromosome(Ph).The Ph chromosome results from a reciprocal translocation between the long arms of chromosome 9 and 22,t(9;22) (q34;q11).The molecular consequence of this translocation is a fusion gene. Imatinib inhibits constitutively active BCR-ABL tyrosine kinase of Chronic Myeloid Leukemia (CML).This is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. We are now report 51 months of median follow-up data and focus on 645 number of patients who received Imatinib as a primary treatment from 2002 to 2010. Materials and Methods: We included total 645 patients of CML during the period of January 2002 to June 2010.The age range was 02–87 years with median age being 36±11.6 years. Among 645 patient 366 was male and 280 female. A total 645 patients 608was in chronic phase, 31 in accelerated phase and 5 patients had blast crisis at the time of presentation. At present the molecular status of the disease has been detected by RT PCR, Flowcytometry (By Fluorescence Activated Cell sorter, FACS), Karyotyping and FISH.As a runtime protocol we have used Imatinib as 400 mg/day as standard dose at chronic phase, 600 mg/day in accelerated phase and 800 mg/day in blast crisis.We have studied a comparative analysis of Hematological parameter values. Result: The best observed average rate of complete hematological response was 97%, complete cytogenetic response was 50%, complete molecular response 35% with partial response in 45% and poor response in 15%.After 1 year levels of BCR-ABL transcripts had fallen in 52% patients and after 4 years levels had fallen in 79%. Conclusion: At 51 months of median follow-up in our study, comparative analysis of haematological parameters like haemoglobin, Total Count, Platelet Count between patient and normal population revels that pre-treatment value against normal value is very significant. The post treatment value of the haematological parameters is very close to the normal values and hence it can be proved that Imatinib therapy is effective. We observed that Imatinib drug is tolarence in case of 90% patients and resistance in about 10 % patient. So, we can conclude that Imatinib is an effective and safe drug for CML patient. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CML patients in blast crisis have breakpoints localized to a specific region of the BCR

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 448-455 ◽  
Author(s):  
K Schaefer-Rego ◽  
H Dudek ◽  
D Popenoe ◽  
Z Arlin ◽  
JG Mears ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Large Area ◽  
Translocation Breakpoints ◽  
Ph Chromosome

Abstract Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between chromosomes 9 and 22. This activates the abl oncogene by moving it from chromosome 9 and combining it with sequence located on chromosome 22. The new fusion gene, with chromosome 22 sequence at its 5′ end and chromosome 9-abl sequence at its 3′ end, generates a new messenger RNA (mRNA) and protein that are implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 are concentrated within a 6 kilobase (kb) region termed the breakpoint cluster region (bcr). This study was designed to determine whether chronic-phase and blast crisis patients had identifiable differences in the structure of their Ph chromosomes. Restriction mapping of the chromosome 22 translocation breakpoints performed for 26 patients showed that the breakpoints of eight of the nine patients in blast crisis were in the 3′ portion of the bcr, whereas the breakpoints in the 17 patients in the chronic phase were clustered in the 5′ portion of the bcr. This suggests a strong correlation between a 3′ bcr breakpoint and blast crisis in CML.

scholarly journals Basophils (Bsp-1+) derive from the leukemic clone in human myeloid leukemias involving the chromosome breakpoint 9q34

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 777-781 ◽  
Author(s):  
MP Bodger ◽  
CM Morris ◽  
MA Kennedy ◽  
JA Bowen ◽  
JM Hilton ◽  
...  
Keyword(s):  
Toluidine Blue ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Interleukin 2 ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Normal Karyotype ◽  
Buffy Coat ◽  
Chromosome 9 ◽  
Leukemic Clone

Abstract The monoclonal antibody (MoAb) Bsp-1 was used to purify basophilic cells from leukemic blood of five patients with Philadelphia chromosome (Ph′) positive chronic myeloid leukemia (CML) and two patients with acute myeloid leukemia (AML) characterized by the chromosomal translocation t(6;9)(p23;q34). When cultured, Bsp-1 positive cells from all CML and AML patients showed the same clonal karyotype changes observed in diagnostic buffy coat preparations, indicating that the basophilic cells were of leukemic origin. In contrast, T lymphocytes from four of five CML patients cultured in the presence of interleukin- 2 (IL-2) showed a normal karyotype and were therefore not derived from the leukemic clone. Bsp-1 staining correlated with toluidine blue- positive basophils in chronic phase CML and with toluidine blue- negative blast cells expressing an immature myeloid phenotype in blast crisis CML and AML. Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients. These results indicate that the breakpoint at 9q34 in CML is 5′ of ABL, whereas the breakpoint at 9q34 in AML is 3′ of ABL. Field inversion gel electrophoresis showed that the 9q34 breakpoint was not within 200 kb 3′ of ABL in one of the AML patients, nor was there any rearrangement of the PIM oncogene locus at 6p21.

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