scholarly journals Clinicopathological Variables and Outcome in Chronic Phase Chronic Myeloid Leukemia Associated with BCR-ABL1 Transcript Type and Obesity

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Mohammad Abdul-Jaber Abdulla ◽  
Prem Chandra ◽  
Susana El akiki ◽  
Claudio Sorio ◽  
Luisa Tomasello ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Normal Weight ◽  
Chromosome 9 ◽  
Response To Treatment ◽  
Study Cohort ◽  
Clinicopathological Variables ◽  
Transcript Type

Introduction Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation. The hallmark of CML is BCR-ABL1 (breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1) on Philadelphia chromosome, which is the result of a reciprocal translocation between the long arms of chromosomes 9 and 22 (t[9;22][q34;q11]). With rare exceptions, breaks in chromosome 22 localize to one of three BCRs and determine the portions of BCR retained in the BCR-ABL1 fusion mRNA and protein. In contrast, the chromosome 9 breaks can occur over a large genetic region, 5′ of ABL1 exon Ib, 3′ of ABL1 exon Ia, or most commonly between the two alternative first ABL1 exons. In an overwhelming majority of CML patients, the break occurs in the major BCR (M-BCR), generating e13a2 or e14a2 fusion mRNAs and a p210BCR-ABL fusion protein. p230BCR-ABL, the largest of the fusion proteins, corresponds to a break in the micro BCR (μ-BCR), an e19a2 fusion mRNA, and is associated with neutrophilic predominance and possibly less aggressive disease. Molecular monitoring of BCR-ABL1 transcript levels following treatment with tyrosine kinase inhibitors (TKIs) is central to the effective clinical management of patients with CML. BCR-ABL1 transcripts measured at standardized time points is used to define responses at key milestones in treatment allowing early signs of poor adherence or resistance to treatment to be detected and allow for early, effective clinical intervention. Objective The aim of this study is to evaluate response to treatment with standard dose TKI in obese and non-obese CML patients together with BCR-ABL1 transcript type Methodology A retrospective analysis of clinicopathological variables and response to treatment was performed for 37 chronic phase CMLs to compare, obese vs normal weight, and BCR-ABL1 transcript type determined at diagnosis. Patients' management and response assessment was done based on ELN 2013 guidelines. Response to treatment was assessed using RT-qPCR analysis of blood calculated on the International Scale (IS). Various statistical methods used, all Statistical analyses were done using statistical packages SPSS 22.0 (SPSS Inc. Chicago, IL) and Epi-info (Centers for Disease Control and Prevention, Atlanta, GA) software. Results The study cohort included 26 males (70.3%) and 11 females (29.7%) with mean age at diagnosis 36.8 years. 59.5% (n=22) expressed an e14a2 transcript, and 40.5% (n=15) an e13a2 transcript, most patients were started on imatinib, then switched either due to toxicity or failure. Median follow-up was 18 months for both transcript types. WBC, platelet counts, spleen size and Sokal scores at diagnosis, both median and Inter-quartile range (IQR) were observed to be higher in e14a2 compared to e13a2 transcript group, and, lower in obese patients compared patients with normal weight. At one year, patients with e13a2 transcript had higher percentage of CCyR (or better) 60% (95% CI 36.6, 80.3%) compared to e14a2 group 46.7% (95% CI 24.8, 69.9%), however this difference was statistically insignificant (odds ratio =1.71, 95% CI 0.40, 7.29; P=0.464) Overall, there was higher and faster achievement of CCyR and MMR in patients with e13a2 transcript compared to e14a2 transcript, and in the obese vs normal-weight patients. Patients in e13a2 group and obesity group had a lower rate of treatment failure and fewer indications to switch TKI. Of note MMR was observed to be significantly higher in patients of African origin (n=10) compared to patients with Asian ethnicity (50% vs 16%; P=0.038), which could be reflect differences in disease biology. Conclusion In the patient cohort studied an e14a2 BCR-ABL1 transcript type / normal body weight was associated with an inferior outcome when compared to e13a2 transcript / obesity groups Disclosures No relevant conflicts of interest to declare.

scholarly journals Multidrug Resistance Gene (MDR1) Polymorphism and Response to Nilotinib in Egyptian Patients with Chronic Myeloid Leukemia (CML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5220-5220
Author(s):  
Mervat Mattar ◽  
Hend Ellithy ◽  
Yasser Elnahas ◽  
Mohamed osman Azzazi
Keyword(s):  
Multidrug Resistance ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Response To Treatment ◽  
Mdr1 Gene ◽  
Molecular Response ◽  
Multidrug Resistance Gene ◽  
Significant Difference

Abstract Introduction: Inappropriate expression of the multidrug resistance (MDR1) gene I in chronic phase chronic myeloid leukemia cases (CML-CP) encodes P glycoprotein (Pgp)that may cause resistance to second generation tyrosine kinase inhibitors (TKIs) Patients and methods: Thirty-one upfront CML-CP patients, planned to receive nilotinib, were included. Detection of MDR1 gene polymorphism C3435T, using PCR Restriction Fragment Length Polymorphisms (PCR-RFLP) was done initially for every patient. We prospectively followed up the patients between February 2012 and February 2014 with PCR for BCR-ABL1 transcripts every 3 months. The molecular response to nilotinib, according to the level of BCR-ABL1 by PCR, was compared to the different MDR1 3435 genotypes. Results: The majority of the patients carried the MDR1 3435CC genotype of Molecular response was optimal in 56%, 60% and 80% of the patients at month 3, 6 and 12 respectively.There was no statistically significant difference between MDR- C3435T genotypes and the molecular response to treatment with nilotinib. Disclosures No relevant conflicts of interest to declare.

scholarly journals Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2304-2309 ◽  
Author(s):  
Jyoti Wadhwa ◽  
Richard M. Szydlo ◽  
Jane F. Apperley ◽  
Andrew Chase ◽  
Marco Bua ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Autologous Transplantation ◽  
Chronic Phase ◽  
Cytotoxic Drugs ◽  
Response To Treatment ◽  
Blastic Transformation ◽  
Factors Affecting ◽  
Hammersmith Hospital ◽  
Blast Cells

We analyzed factors having an impact on response to treatment and survival in 78 consecutive patients with chronic myeloid leukemia (CML) in blastic transformation (BT) referred to the Hammersmith Hospital from January 1995 to December 2000. BT was defined as the presence of at least 30% blasts in blood or marrow or extramedullary blastic deposits. Immunophenotyping of blasts showed 57 myeloid, 19 lymphoid, and 2 biphenotypic. The median age of the patients was 39.1 years (range, 11.3-73.4 years), with 55 males and 23 females. The median survival for all patients after onset of BT was 8.2 months (95% CI, 6.4-10). Patients in lymphoid BT survived longer than those in myeloid BT (median, 11.2 months versus 6.9 months, P = .052). Initial treatment varied; 41 patients received cytotoxic drugs, 8 underwent allogeneic or autologous transplantation procedures, 21 received STI571 (imatinib mesylate, Gleevec), 1 received radiotherapy, and 7 received no therapy. Of the 25 (32%) patients who achieved a “second chronic phase” with first therapy, 6 of 21 (29%) were treated with STI571 and 19 of 50 (38%) were treated with chemotherapy, transplantation, or radiotherapy. Patients who achieved a second chronic phase survived longer than those who did not (median time from onset of BT 12.0 months versus 6.3 months, P = .0004). In multivariate analysis the finding of more than 50% blast cells in the blood and the presence of cytogenetic progression were independent adverse prognostic variables for survival. We conclude that survival after onset of BT has improved in recent years but is still unsatisfactory. We speculate that the combined use of STI571 with cytotoxic drugs may offer additional benefit.

Results of Imatinib Dose Escalation After 36 Months of Follow-up in Chronic Myeloid Leukemia Patients with Failure or Sub-Optimal Response According to 2006 EuropeanLeukemia Net (ELN) Criteria.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3302-3302
Author(s):  
Massimo Breccia ◽  
Fabio Stagno ◽  
Roberto Latagliata ◽  
Paolo Vigneri ◽  
Laura Cannella ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Acquired Resistance ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response

Abstract Abstract 3302 Poster Board III-190 Introduction Imatinib mesylate (IM) given at a daily dose of 400 mg currently represents the gold standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CP). European LeukemiaNet (ELN) guidelines propose IM dose escalation to rescue those CML patients with either suboptimal response or drug resistance. We report on the long-term efficacy of IM dose escalation in 74 patients with CP-CML after suboptimal response or failure to IM conventional dose. Patients and methods Median age was 50 years (range 19-85), there were 52 males and 22 females. Thirteen patients were classified as hematologic failure (10 primary and 3 secondary), 57 patients as cytogenetic resistance (24 primary and 33 acquired). Three patients escalated the dose for cytogenetic suboptimal response and one patient for molecular suboptimal response at 18 months. Fifty-four received IM dose escalation from 400 to 600 mg and 20 patients from 400 to 800 mg. Results Overall, after a median follow-up of 36 months, 68/74 (91.8%) patients maintained or achieved a complete haematologic response (CHR); this was maintained in all patients who escalated the dose for cytogenetic failure or suboptimal response. A major cytogenetic response (MCyR) was achieved in 41 patients (72%) who escalated the dose for cytogenetic failure and in 6/13 (46%) patients who escalated imatinib for hematologic failure (p=0.002). Overall, complete cytogenetic responses (CCR) were achieved in 27 (37%) out of 74 CML patients: of the 13 hematologic failure patients, only 5 achieved CCyR: all patients had prior acquired resistance to imatinib. Of the 57 cytogenetic failure, 22 reached CCR: this response was obtained in 27% of the primary cytogenetic resistant, and in 50% of the acquired cytogenetic resistant patients (p=0.02). Three patients who escalated the dose for cytogenetic suboptimal response obtained CCR and complete molecular response (CMR), whereas one patient who escalated the dose for molecular suboptimal response at 18 months did not obtain CMR. Median time to cytogenetic response was 3.5 months. Cytogenetic responses occurred in 37/50 patients who escalated the dose to 600 mg and in 10/20 patients who escalated to 800 mg daily (p=0.234). CMR was obtained in 10 patients: in 7 patients who escalated the dose for cytogenetic failure and in 3 patients who escalated imatinib for suboptimal cytogenetic response. Estimated 2 year-progression free survival (PFS) and overall survival (OS) is 87% and 85% respectively. Sixteen patients (21.6%) experienced toxicities and had temporarily IM interruption. Conclusions Imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic resistance and a prior suboptimal cytogenetic response to standard-dose imatinib, whereas it appears less effective in haematologic failure patients or in molecular sub-optimal responders. The availability of second generation TKI should be taken into account in these letter categories of patients. Disclosures No relevant conflicts of interest to declare.

Cytogenetic Analysis of 1863 Chineses Patients with Chronic Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4888-4888
Author(s):  
Qitian Mu ◽  
Qiuling Ma ◽  
Yungui Wang ◽  
Xiangmin Tong ◽  
Zhimei Chen ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Monocytic Differentiation ◽  
Granulocytic Differentiation ◽  
Monosomy 7

Abstract Abstract 4888 Background: Cytogenetic analyses of chronic myeloid leukemia (CML) have been performed previously in a large number of reports, but systematical research based on large sample sizes is seldom available. In order to further elucidate the cytogenetic nature of CML, we analyzed retrospectively the cytogenetic profiles of 1863 Ph/BCR-ABL-positive CML patients from a research center in China. Results: Of 1266 newly diagnosed CML patients, the median age was 41 years, which is younger than the median age of diagnosis in western populations. The incidence of additional chromosome abnormalities(ACAs) was 3.1% in newly-diagnosed chronic phase(CP), 9.1% in CP after therapy, 35.4% in accelerated phase(AP) and 52.9% in blast phase(BP), reflecting cytogenetic evolution with CML progression. 5.3% patients harbored a variant Ph translocation. A higher prevalence of ACAs was observed in variant Ph translocations than in classical t(9;22) in the disease progression, especially in BP(88.2% vs. 50%, p=0.002). Moreover, a hyperdiploid karyotype and trisomy 8 were closely correlated with myeloid blast crisis(BC) while a hypodiploid karyotype and monosomy 7 were associated with lymphoid-BC. Among subsets of myeloid-BC, compared with myeloid-BC with granulocytic differentiation or monocytic differentiation, myeloid-BC with minimal differentiation had higher ACAs rate (80% vs.46.8%, p=0.009 and 80% vs. 42.9%, p=0.006). Conclusion: CML tends to afflict younger population in China. In the disease progression, the incident of ACAs was higher in variant Ph translocations than in classical t(9;22). Among subsets of myeloid-BC, myeloid with minimal differentiation had distinct cytogenetic features. Disclosures: No relevant conflicts of interest to declare.

Delayed Cytogenetic Response and Reduced Rate of Major Molecular Response Associated to Increased Body Mass Index At Baseline in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Imatinib.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2784-2784
Author(s):  
Massimo Breccia ◽  
Giuseppina Loglisci ◽  
Adriano Salaroli ◽  
Alessandra Serrao ◽  
Paola Volpicelli ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Body Mass ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Normal Weight ◽  
First Line ◽  
Reduced Rate ◽  
The Impact

Abstract Abstract 2784 Obesity, measured as body mass index (BMI), has been identified as a possible risk factor for the onset of several solid tumors as well as for chronic myeloid leukemia (CML). To date, no correlations have been reported in this latter disease between BMI at baseline and response to targeted therapies. We refer here on the impact of BMI on clinical response in CML. Three hundred and thirty-nine chronic phase (CP) CML patients treated with imatinib entered the study: 142 patients first received interferon alpha outside clinical trials and were then switched to imatinib for failure. For this group of patients, BMI was collected at the time of start of imatinib. The remaining patients were consecutively treated with imatinib first-line from January 2000 onward. BMI was defined as the individual's body weight divided by the square of his of her height and patients were categorised according to WHO into four categories: underweight (BMI < 18.5), normal weight (BMI 18.5-< 25), overweight (BMI 25-<30) and obese (BMI ≥ 30). All patients were followed according to ELN guidelines. We also analysed 25 CP-CML patients treated frontline with nilotinib. One hundred and fifty-six patients (46%) were categorized as underweight/normalweight, while 183 patients (54%) were classified as overweight/obese. BMI increased with age, with a median age of 29 years in underweight category, 43.4 years in normal weight, 54.9 years in overweight and 62.4 years in obese patients (p=0.001). We did not reveal statistically significant association between BMI and prognostic risk stratification at baseline, even when we used new EUTOS score, or type of BCR/ABL transcript. No statistically significant difference was revealed in terms of overall CCyR rate which was 87% for underweight/normal weight categories compared to 84% for overweight/obese group (p=0.34). If compared to patients with low BMI (< 18.5–25), patients with increased BMI (> 25–40) at diagnosis who received imatinib, showed a significantly longer median time to reach CCyR (6.8 months vs 3.3 months, p=0.01), a reduced rate of MMR (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.03). At 18 months, molecular kinetics revealed that median BCR-ABL/ABL ratio was 0.6% IS (range 0.001%-2%) in underweight/normal weight group compared to 1.6% IS (range 0.01%-3%) in overweight/obese category (p=0.01). Conversely, no differences were revealed with respect to BMI in patients treated frontline with nilotinib and also patients with increased BMI obtained rapidly CCyR and MMR, with an incidence similar to that of underweight/normal weight patients. These results suggest that CML patients with increased weight at baseline should be followed and carefully monitored if treated with standard dose imatinib frontline for a possible early switch to a second generation TKI or, as an alternative, should preferably be candidate to receive these drugs as a first line therapy. Disclosures: No relevant conflicts of interest to declare.

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.

Therapeutic Immune Monitoring of Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors: Focus on CD4+ CD25+ t Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4036-4036
Author(s):  
Ziyuan Lu ◽  
Na Xu ◽  
Xuan Zhou ◽  
Guanlun Gao ◽  
Lin Li ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Similar Proportion

Abstract Background and Objectives: In clinical, conventional Tyrosine Kinase Inhibitors (TKIs) including imatinib, dasatinib, and nilotinib are remarkably effective forms of therapy for certain types of solid cancers as well as Ph+ leukemias. In addition to the BCR-ABL target oncoprotein, they also inhibit certain off-target kinases (Eph, c-KIT, TEC, SRC). Some TKIs affect immune reconstitution as well as the proliferation, function, and activation of T cells. Certain TKIs have been known to have an especially strong effect on CD4+CD25+ T cells, also known as regulatory T Cells (Tregs). There is currently a gap in the clinical data available about on this area of study. Patients and methods: In this study, we collected 108 Peripheral Blood (PB) samples from patients in the Chronic Phase (CP) of Chronic Myeloid Leukemia (CML) at the time of diagnosis (n=31) and also the TKIs treatment. Groups consisted of individuals treated with TKIs like imatinib (n=12), dasatinib (n=11) and nilotinib (n=8), as well as healthy controls (n=15). We evaluated the quantity and function of Tregs from patients in the CML-CP at the time of diagnosis and during treatment with TKIs. Results: It was found that at diagnosis, patients with CML had a similar proportion and absolute number of lymphocytes compared to healthy donors. After TKIs treatment, proportions and absolute numbers of total T cellsACD4+ T cells and Tregs decreased at different degree. Moreover, thedecrease would be more and more significant as time goes on.Our results indicated that although these three TKIs show similar inhibitory effects in the proportion and number of Tregs in vivo, they have differential effects on the functions of Tregs in vitro. The proliferation, suppression, and expression of suppressive cytokines (IL-4,IL-10 and TGF-β) as well as suppression-associated molecules (FoxP3, GITR, and CTLA-4) of Tregs decreased in groups treated with imatinib and dasatinib. The decrease was not significant in the nilotinib-treated group. Conclusions: The results showed that imatinib and dasatinib have stronger inhibitory roles than nilotinib when it comes to regulating the number and functions of Tregs. These findings can be used to argue in favor of calls for personalized treatment and follow-up of CML patients during TKIs treatment, particularly for those patients who received combination therapy with allo-transplantation and post-transplant TKIs. Disclosures No relevant conflicts of interest to declare.

How I treat chronic myeloid leukemia in the imatinib era

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2828-2837 ◽  
Author(s):  
John M. Goldman
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Initial Treatment ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Response To Treatment ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Allogeneic Transplant ◽  
Reduced Intensity Conditioning ◽  
Log Reduction

AbstractAlthough it is now generally accepted that imatinib is the best initial treatment for patients newly diagnosed with chronic myeloid leukemia (CML) in chronic phase, a number of questions remain unanswered. For example, (1) Is imatinib the best initial treatment for every chronic-phase patient? (2) At what dose should imatinib be started? (3) How should response to treatment be monitored? (4) For how long should the drug be continued in patients who have achieved and maintain a complete molecular response? (5) How does one handle a patient who achieves a 2-log but not a 3-log reduction in BCR-ABL transcripts? (6) How should response or failure be defined? (7) For the patient deemed to have failed imatinib, should one offer dasatinib or nilotinib? (8) For the patient who has failed imatinib but has a possible allogeneic transplant donor, should one offer dasatinib or nilotinib before recommending a transplantation? (9) Should the transplantation be myeloablative or reduced intensity conditioning? (10) How should one treat the patient who relapses after allografting? This paper will address these issues, many of which cannot yet be answered definitively.

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.

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