Duplication of chromosome 9 carrying a BCR/ABL chimeric gene in Philadelphia chromosome negative chronic myeloid leukemia

1996 ◽  
Vol 89 (2) ◽  
pp. 166-169 ◽  
Author(s):  
Naoto Takahashi ◽  
Ikuo Miura ◽  
Atsushi Ohshima ◽  
Seiko Utsumi ◽  
Takashi Nimura ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chimeric Gene ◽  
Chromosome 9

THE CASE VARIANT TRANSLOCATION T(3;9;22)(P24;Q34;Q11) IN CHRONIC MYELOID LEUKEMIA

2018 ◽  
Vol 64 (6) ◽  
pp. 810-814
Author(s):  
Kodirzhon Boboev ◽  
Yuliana Assesorova ◽  
Kh. Karimov ◽  
B. Allanazarova
Keyword(s):  
Adverse Effect ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Genetic Locus ◽  
Philadelphia Chromosome ◽  
Chromosome 9 ◽  
Banding Technique ◽  
Variant Translocation

This paper presents a case of chronic myeloid leukemia with an earlier unknown variant translocation t (3; 9; 22) (p24; q34; q11) detected by cytogenetic research using the GTG-banding technique. Despite the absence of the classical Philadelphia chromosome, the presence of chromosome 9 and 22 derivatives, as well as the BCR-ABL fusion gene, allow this translocation to be considered pathogenetic for CML. A good response of the patient to the treatment with glivec is that there is no adverse effect on the pathogenesis of the disease of an additional genetic locus (3p24) involved in complex restructuring.

A Translocation (9;22)(p24;q11.2) In a Patient With CML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5184-5184
Author(s):  
Daniele Costa Abreu ◽  
Ana Paula Castilho, Bachelor ◽  
Vivian Dionísio Niewiadonski, Bachelor ◽  
Mauricio Drummond ◽  
Nelson Gaburo
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Medical Information ◽  
Conflicts Of Interest ◽  
Philadelphia Chromosome ◽  
Chromosome Analysis ◽  
Chromosome 9 ◽  
Fish Analysis ◽  
Ph Chromosome

Abstract Introduction In January 2013 was received in our lab service a bone marrow sample for cytogenetic analysis. The 61 years old female patient presents an elevated white blood cell count (118,000 x10³/mm³) and clinical diagnosis as Chronic Myeloid Leukemia (CML). According the medical information the treatment began with hydroxyurea 3g daily and allopurinol 300mg daily. Methods We proceeded with cytogenetic examination of the patient’s bone marrow aspirate by conventional G-banding analysis performed on unstimulated short-term cultures (24 hrs). FISH for BCR/ABL translocation was tested using a dual fusion dual color probe. Because of the sample stability we were unable to performed RT-PCR test. Results Chromosome analysis showed the translocation (9;22)(p24;q11.2) as a sole abnormality in 100% (20/20) of analyzed metaphases. Chronic myeloid leukemia presents as a specific chromosomal abnormality the Philadelphia chromosome, t(9;22)(q34;q11) which is different from the results obtained where the region of translocation of chromosome 9 was p24 instead of the classic q34. This result suggests it is BCR/JACK2 translocation. The FISH analysis showed the presence of a complex Ph chromosome: ABL con BCRx1 (one fusion) and BCRx2;ABLx2. Conclusion The patient took imatinib without answer. She is still in clinical monitoring with persistent hyperleucocytosis and the treatment is following with hydroxyurea 500mg daily and Interferon 5000 UI three times a week. Further molecular and cytogenetic tests will be performed in a second sample to contribute with evaluation of disease progression and monitoring treatment response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Detection of the BCR-ABL Gene By the Real-Time PCR Method in Patients with Chronic Myeloid Leukemia in Rio Grande Do Norte, Brazil

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5432-5432
Author(s):  
Aldair Sousa Paiva ◽  
Hugo Diogenes De Oliveira Paiva ◽  
Geraldo Barroso Cavalcanti ◽  
Gioconda DR Leão ◽  
Marcos Dias Leão ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real Time ◽  
Real Time Pcr ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Rna Extraction ◽  
Philadelphia Chromosome ◽  
Genetic Material ◽  
Chromosome 9 ◽  
The Real

Abstract Background: The Philadelphia chromosome is a cytogenetic change resulting from a reciprocal translocation of genetic material between ABL genes from chromosome 9 and BCR from chromosome 22 or t(9; 22) (q34; 11), forming the chimeric gene BCR- ABL, being associated with chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). The p190 variant is usually associated with acute forms of leukemia, including AML and ALL, whereas the p210 variant is associated with the chronic phases of CML. Due to the high sensitivity and specificity, nucleic acid amplification techniques by real-time PCR have replaced the conventional cytogenetic techniques for the identification of the Philadelphia chromosome and its p190 and p210 variants. Molecular analysis has been indicated in the initial diagnostic phase and also for the therapeutic monitoring defining the percentage of neoplastic cells present in the patients during the different phases of the treatment (Minimum Residual Disease or MRD).The aim of this study was the transcript BCR-ABL identification in patients with suspected of CML and evaluation of the gene frequency in these patients. Methods: The presence of BCR-ABL gene was investigated in blood samples from 42 patients with suspected CML. The RNA extraction was performed by phenol/chloroform method. The cDNA was submitted to PCR, using specific primers for and BCR-ABL genes by Real time PCR. Results: From all studied patients, 16 (38.10%) were negative, and 26 (59.09%) positive for one of rearrangements: p210 b3a2 and b2a2 in 18 cases (40.91%) and p190 a1a2 in 2 cases (4,76%) and double positive p120/190 in 6 cases (14,28%). We observed that the most common rearrangement was the p210 b3a2, and the molecular results were compatible with clinical and hematologic suspicion. Conclusions: The Real-timePCR, because of its specificity and sensitivity, can be considered the most used technique in routine diagnosis and investigation of MRD of CML patients. Disclosures No relevant conflicts of interest to declare.

Highly Sensitive Fluorescence In Situ Hybridization Method to Detect Double BCR/ABL Fusion and Monitor Response to Therapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3357-3365 ◽  
Author(s):  
Gordon W. Dewald ◽  
William A. Wyatt ◽  
Amy L. Juneau ◽  
Richard O. Carlson ◽  
Alan R. Zinsmeister ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Ph Chromosome ◽  
Cytogenetic Remission

Abstract We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

BCR/ABL Fusion Gene On Constitutional Der(14;22) Roberstsonian Translocation in a Case of Chronic Myeloid Leukemia with Masked Philadelphia Chromosome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4822-4822
Author(s):  
Pablo Lopez ◽  
Daniela Infante ◽  
Isabel Moro ◽  
Victoria Elizondo ◽  
Gerardo Romanelli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Cytogenetic Analysis ◽  
Myeloid Leukemia ◽  
Robertsonian Translocation ◽  
Philadelphia Chromosome ◽  
Chromosome 9 ◽  
Ph Chromosome ◽  
One Step

Abstract Abstract 4822 Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome (Ph) observed in more than 90% of patients with CML as a result of t(9;22)(q34;q11), leading to the formation of the BCR/ABL chimeric gene. The remaining 5–10% of CML cases exhibit a variant Ph translocation generally involving a third or even a fourth chromosome in addition to chromosome 9 and 22, potentially leading to masked Ph chromosome or reveal cryptic translocations that remains undetected under conventional cytogenetic analysis. These chromosome rearrangements can be disclosed by means of fluorescence in situhybridization (FISH) or polymerase chain reaction (PCR) procedures. A very few Ph positive CML cases were reported with constitutional robertsonian translocations, i.e. translocation between two acrocentric chromomosomes (13–15, 21–22), with breakpoints in the short arms, leading to a dicentric chromosome and thus to 45 instead of 46 chromosomes Case Report. 42 year-old woman presenting with asthenia. Physical examination: Grade 1 splenomegaly. Peripheral blood count showed: hemoglobin concentration 117g/L, platelet count: 329×109/L and white blood cell count (WBC): 199×109/L. Peripheral blood smear: myelemia exhibiting 3% of myeloid blasts. Cytogenetic analysis by G-banding performed on bone marrow metaphase cells afforded the following karyotype: 45, XX, der(14;22)(q10;q10)c?, t(9;22;11)(q34;q11;q13) [20]. The analysis of the BCR-ABLfusion gene according to standard protocols detected the presence of the b3a2 isoform. FISH studies using dual color dual fusion probes in metaphases showed a 1F2G2R signal pattern. We detect a normal ABL signal on chromosome 9 and BCR signal on chromosome 22; the fusion signal was present on the der(14;22);extra-signals BCR and ABL with reduced intensities were present on der(11) and der(9) respectively: ish der(9)(ABLdim+), der(11)(BCRdim+), der(14;22)(BCR+,ABL+) [10]. FISH analysis on interphase nuclei (n=200) presented the same signal pattern. Nuc ish (ABL, BCRx3)(BCR con ABL x1) [200]. Chromosome analysis of bone marrow cells after six months of Imatinib therapy showed the following karyotype: 45, XX, der(14;22)(q10;q10)c [20] thus demonstrating complete cytogenetic remission and that der(14;22) is a robertsonian constitutional abnormality that could be inherited and thus necessitate a familial genetic councelling to inform about the familial risk of congenital malformations and miscarriage. Discussion. To explain the formation of variant chromosome Ph translocations one-step, two-step and multi-step mechanisms have been proposed. In our case complex translocations involving four chromosomes and the participation of two acrocentric chromosomes, led to the hypothesis of the presence of a constitutional or acquired Robertsonian translocation. Karyotype analysis six months after treatment confirmed the presence of a constitutional Robertsonian translocation. According to the FISH pattern, this variant Ph chromosome was formed in one step. The occurrence of Philadelphia positive CML in a patient with a constitutional Robertsonian translocation is probably coincidental. The role of constitutional chromosomes abnormalities in hematologic malignancies is well known in Down syndrome patients and in chromosome breakage syndromes such as Fanconi anemia. In the literature, only one case of CML patients with Robertsonian t(14;22) have been described. To our knowledge this is the first report showing a Robertsonian t(14;22) in a variant Ph involving four chromosomes and exhibiting the fusion FISH signal in a derivative chromosome 14, with masked Ph. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Rare Case of Pericentric Inversion, Inv(9)(p13q34) of the Der(9)t(9;22)(q34;q11) in A Patient with Chronic Myeloid Leukemia – A Case Report

2021 ◽  
Vol 3 (6) ◽  
pp. 13-16
Author(s):  
Semir Mešanović ◽  
Haris Šahović ◽  
Maja Konrad Ćustović ◽  
Damir Sabitović
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Pericentric Inversion ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Fusion Transcript ◽  
Chromosome 9 ◽  
Specific Marker ◽  
Hematological Disease ◽  
Polymerase Chain

As we know, the Philadelphia chromosome (Ph) is a highly specific marker for chronic myeloid leukemia (CML). This hematological disease is characterised by the formation of the BCR/ABL1 fusion gene, usually with typical translocation pattern including 9q34 and 22q11. In this paper we describe a 55 years old female patient with typical clinical and haematological signs of CML and a chromosome 9 differing from that which normally participates in translocation t(9;22). The karyotype of this Ph positive patient is characterised by pericentric inv(9)(p13q34) of the der(9)t(9;22)(q34;q11). Reverse transcriptase-polymerase chain reaction revealed a e14a2 type of BCR/ABL1 fusion transcript. As a consequence of this unusual translocation, FISH also found the separation of the ABL1/BCR1 fusion gene on chromosome 9. On reviewing the literature, to date only 10 Ph-positive leukemia patients have been noticed to have pericentric inversion inv(9)(p22q34)der(9)t(9;22)(q34;q11). No one case has been described with pericentric inversion inv(9)(p13q34) of the der(9)t(9;22)(q34;q11). This indicate that pericentric inv(9)(p13q34) of the der(9)t(9;22)(q34;q11) is a novel, rare, chromosomal abnormality in Ph-positive CML.

scholarly journals Highly Sensitive Fluorescence In Situ Hybridization Method to Detect Double BCR/ABL Fusion and Monitor Response to Therapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3357-3365 ◽  
Author(s):  
Gordon W. Dewald ◽  
William A. Wyatt ◽  
Amy L. Juneau ◽  
Richard O. Carlson ◽  
Alan R. Zinsmeister ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chronic Myeloid Leukemia ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Chromosome 9 ◽  
Ph Chromosome ◽  
Cytogenetic Remission

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

scholarly journals Significance of bcr-abl molecular detection in chronic myeloid leukemia patients

JMS SKIMS ◽  
2016 ◽  
Vol 19 (2) ◽  
pp. 95-96
Author(s):  
Manzoor A Malik
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Detection ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Chromosome 9 ◽  
Chromosome 1 ◽  
Chromosome 22 ◽  
Myeloproliferative Disease ◽  
Region Gene

Important advances in the understanding of the molecular basis of chronic myeloid leukemia have resulted in the development of new therapies and changed the paradigm for managing this myeloproliferative disease. The reciprocal translocation of the abl (Abelson murine leukemia) proto-oncogene on chromosome 9 to the bcr (breakpoint cluster region) gene on chromosome 22 creates a transcriptionally active, chimeric bcr-abl gene and gives rise to the Philadelphia chromosome. 1 The genetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome (Ph), which occurs in at least 95% of CML cases as well as some cases of acute lymphocytic leukemia (ALL; approximately 5% for children, 20% for adults). It also has been reported in some other hematologic disorders, albeit rarely. 2-4  JMS 2016; 19(2):95-96 

scholarly journals CHRONIC MYELOID LEUKEMIA IN PREGNANCY

2018 ◽  
Vol 24 (3) ◽  
pp. 286
Author(s):  
Rosa Dwi Wahyuni ◽  
Agus Alim Abdullah ◽  
Mansyur Arif
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Peripheral Blood Smear ◽  
Chromosome 9 ◽  
Translocation Chromosome ◽  
Laboratory Evaluation ◽  
Abnormal Growth ◽  
In Pregnancy

Chronic Myeloid Leukemia (CML) is one of leukemias characterized by abnormal growth of myeloid cells in bone marrow. The Philadelphia chromosome is diagnostic parameter for CML. This chromosome is t(9;22) (q32;q21), a translocation chromosome 9 and 22 relocates a portion of proto-oncogene c-ABL from chromosome 9 to BCR on chromosome 22. Chronic myeloid leukemia consisting of three phases; Chronic, Accelerating and the Blast crisis phase. The clinicaling symptoms of CML are hypercatabolism, splenomegaly, anemia, bruising and sign of Gout. Chronic myeloid leukemia in pregnancy shows a better prognosis than acute leukemia in pregnancy. Chronic myeloid leukemia has the risk of leukocytosis which can lead to uteroplacental insufficiency giving rise to various consequences: fetal growth retardation and perinatal mortality. Moreover, the therapy of CML should be carefully administered considering the fetal effects.  Both sexes have the same risk, mostly in the range of 40 to 60 years old. In this case report, a 38-year-old pregnant female (G1P0A0) with 37 weeks of gestational age was diagnosed as CML on August 2013 and was treated with 500 mg of Cytodrox/Hydroxyurea twice to three times a day until January 2014. Laboratory evaluation on November 10th, 2014, showed leucocytes 449500/µL, erythrocytes 2.58.106/µL, hemoglobin 8.0 g/dL, thrombocytes 437,000/µL and hematocrit 23%. The peripheral blood smear showed normocytic normochromic erythrocytes, anisocytosis, ovalocytes, significantly increased leucocyte count, predominance polymorphonuclear series, all maturation series of myelocytes, 7% myeloblast, normal thrombocyte count and morphology. Based on these evaluations, the patient was diagnosed as CML. The evaluation of Neutrophil Alkaline Phosphatase (NAP) scored 1.

Sign in / Sign up

Export Citation Format

Share Document