Chronic myeloid leukemia with variant e19a2 BCR-ABL1 fusion transcript: interest of the molecular identification at diagnosis for minimal residual disease follow-up

2014 ◽  
Vol 72 (3) ◽  
pp. 359-366
Author(s):  
Nicolas Gendron ◽  
Nabila Belhouachi ◽  
Véronique Morel ◽  
Zahia Azgui ◽  
Karim Maloum ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Molecular Identification ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Fusion Transcript ◽  
Minimal Residual

scholarly journals Manifold-assisted Reverse Transcription-PCR with Real-Time Detection for Measurement of the BCR-ABL Fusion Transcript in Chronic Myeloid Leukemia Patients

2000 ◽  
Vol 46 (7) ◽  
pp. 913-920 ◽  
Author(s):  
Gisela Barbany ◽  
Anette Hagberg ◽  
Ulla Olsson-Strömberg ◽  
Bengt Simonsson ◽  
Ann-Christine Syvänen ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real Time ◽  
Minimal Residual Disease ◽  
Reverse Transcription ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Detection System ◽  
Fusion Transcript ◽  
Mrna Quantification ◽  
Minimal Residual

Abstract Background: BCR-ABL fusion mRNA expression in bone marrow or peripheral blood can be used as a measure of minimal residual disease in patients with chronic myeloid leukemia (CML). Methods: We used an oligo(dT)-coated manifold support to capture the mRNA directly from the cell lysate. After reverse transcription, the cDNA was eluted from the manifold support, and BCR-ABL and GAPDH mRNAs were quantified in real time using the TaqMan fluorogenic detection system. Results: The detection limit of the method was one positive K562 cell among 105 negative cells. GAPDH was chosen as a reference gene based on the low variation between samples from different stages of the disease and the low signal in the absence of reverse transcription. The day-to-day variation of the method (CV) was 32%. In 43 blood samples from 13 CML patients, mRNA quantification agreed well with cytogenetic data. Conclusions: The proposed procedure constitutes a reproducible and sensitive BCR-ABL mRNA quantification method and is suitable to monitor minimal residual disease in CML patients.

scholarly journals Treatment-free remission in Chronic Myeloid Leukemia harboring atypical BCR-ABL1 transcripts.

2020 ◽  
Vol 12 (1) ◽  
pp. e2020066 ◽  
Author(s):  
Matteo Dragani ◽  
Jessica Petiti ◽  
Giovanna Rege-Cambrin ◽  
Enrico Gottardi ◽  
Filomena Daraio ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Digital Pcr ◽  
Treatment Free Remission ◽  
Minimal Residual

Discontinuation of tyrosine kinase inhibitors (TKI) is the main goal today in the field of Philadelphia positive chronic myeloid leukemia (Ph + CML) and the criteria to attempt the interruption of therapy are well defined and rely on the possibility to regularly monitor the BCR-ABL1 transcript. Patients harboring atypical transcripts are automatically excluded from protocols due to the absence of a standardized method of quantification of their minimal residual disease (MRD). We report here the outcome of 6 patients with atypical transcripts with a long follow up whose MRD was followed in three cases with digital PCR during their treatment free remission (TFR).

Monitoring Minimal Residual Disease by Quantitative PCR in Chronic Myeloid Leukemia Patients in Complete Cytogenetic Remission

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4272-4272
Author(s):  
Carolina Pavlovsky ◽  
Isabel Giere ◽  
Virginia Lombardi ◽  
Pedro Negri ◽  
Beatriz Moiraghi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Transcript Levels ◽  
Minimal Residual

Abstract The landscape of chronic myeloid leukemia (CML) has radically changed since the introduction of tyrosine kinase inhibitor (TKI), imatinib (IM), now considered as standard therapy. Although excellent cytogenetic responses are obtained, minimal residual disease still persists in a proportion of patients (pts) when measured by serial molecular monitoring by quantitative real-time polymerase chain reaction (RQ-PCR) to measure BCR-ABL transcript levels (Baccarani M et al. Blood2006; 108:1809–20). We monitored BCR-ABL transcript levels by RQ-PCR in 176 chronic phase (CP) –complete cytogenetic response (CCyR) CML pts treated with IM. Median follow-up from start of therapy with IM was 35 (6–80) months. Pts were recruited from 33 centers in Argentina and 2 in Uruguay. Median follow up from the first assessment at our Institution was 18 (6–32) months. Seventy nine patients (45%) had received interferon as 1st line prior to IM and 97/176 (55%) pts received imatinib as 1st line. Eighty eight percent (155/176) pts had received IM 400mg/d and 12% (21/176) 600–800mg at study initiation. Fifty four percent presented with low Sokal score at diagnosis. Peripheral blood samples were tested by RQPCR every 6 months. Major molecular response (MMR) was defined as BCR-ABL/ABL ratio of <0,1% on the Internationale Scale. Rise in transcript levels was immediately reconfirmed. Cytogenetic and mutational analyses were performed if rise in transcripts was confirmed. Overall, 48% had MMR at the initial evaluation (baseline), and this increased to 57% at last follow-up (month 18). No patient with MMR achievement lost CCyR. Only 5 pts lost CCyR, never having achieved MMR (p=0.01). All patients could be divided in 3 groups according to transcript level outcome: 61% decline (at least 1 log reduction of BCR-ABL/ABL ratio), 27% stable (no log variation), 13% rise (increasing 1 log of BCR-ABL/ABL ratio). Among 136 pts with follow up at month 18, we observed (Table 1): Molecular Response At baseline Decline in transcript levels %(pts) Stable transcript levels %(pts) Rise in transcript levels %(pts) Total %(pts) CMR: complete molecular response, U: undetectable CMR ≥ 4 log red <0,01%/U MMR ≥ 3 log red < 0,1% (N:60) 20(12) 63(38) 17(10) 44(60) No MMR > 0,1% (N:76) 47(36) 47(36) 5(4) 56(76) Total 35 (48) 55(74) 10(14) 100(136) From the group of pts with rise in transcript levels, 5 pts lost CCyR, none lost complete hematologic response. Overall, 5%(9/176) pts eventually changed therapy to a 2nd generation TKI: 5 pts with cytogenetic relapse and 4 pts with increase in transcript levels. Our results confirm that molecular responses continue improving over time and a significant number of pts achieve undetectable transcript levels with continued imatinib therapy. Achievement of MMR is associated with sustained cytogenetic response. These results emphasize the validity and feasibility of molecular monitoring in all areas of the world.

Endogenous Erythroid Colony Formation in Chronic Myeloid Leukemia: A Recurrent Finding Associated with Persistent Minimal Residual Disease Under Imatinib

2013 ◽  
Vol 22 (23) ◽  
pp. 3043-3051 ◽  
Author(s):  
Elisa Einwallner ◽  
Eva Jaeger ◽  
Gerlinde Mitterbauer-Hohendanner ◽  
Martin Bilban ◽  
Ingrid Simonitsch-Klupp ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Colony Formation ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Minimal Residual

scholarly journals Immunophenotyping Investigation of Minimal Residual Disease Is a Useful Approach for Predicting Relapse in Acute Myeloid Leukemia Patients

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2465-2470 ◽  
Author(s):  
J.F. San Miguel ◽  
A. Martı́nez ◽  
A. Macedo ◽  
M.B. Vidriales ◽  
C. López-Berges ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Rhodamine 123 ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract A high complete remission rate is currently achieved in patients with acute myeloid leukemia (AML). However, many patients eventually relapse due to the persistence of low numbers of residual leukemic cells that are undetectable by conventional cytomorphologic criteria (minimal residual disease [MRD]). Using immunophenotypic multiparametric flow cytometry, we have investigated in sequential studies (diagnosis and follow-up) the impact of MRD detection on the outcome of 53 AML patients that had achieved morphologic remission with standard AML protocols and displayed at diagnosis an aberrant phenotype. Patients were studied at diagnosis with a panel of 35 monoclonal antibodies in triple staining combinations for detection of aberrant or uncommon phenotypic features. According to these features, a patient's probe was custom-built at diagnosis for the identification of possible residual leukemic cells during follow-up. The level of MRD at the end of induction and intensification therapy correlated with the number of relapses and relapse-free survival (RFS). Thus, patients with more than 5 × 10−3 residual cells (5 residual cells among 1,000 normal bone marrow [BM] cells) identified as leukemic by immunophenotyping in the first remission BM showed a significant higher rate of relapse (67% v 20% for patients with less than 5 × 10−3 residual cells; P = .002) and a lower median RFS (17 months v not reached; P = .01). At the end of intensification, with a cut-off value of 2 × 10−3 leukemic cells, AML patients also separated into two distinct groups with relapse rates of 69% versus 32% (P = .02), respectively, and median RFS of 16 months versus not reached (P = .04). In addition, overall survival was also significantly related to the level of residual cells in the marrow obtained at the end of induction and particularly after intensification therapy (P = .008). Furthermore, we have explored whether residual disease was related with the functional expression of multidrug resistance (MDR-1) at diagnosis as assessed by the rhodamine-123 assay. Patients with ≥5 × 10−3 residual leukemic cells at the end of induction therapy had a significantly higher rhodamine-123 efflux (mean, 56% ± 24%) than those with less than 5 × 10−3 residual cells (mean, 32% ± 31%; P = .04). Finally, multivariate analysis showed that the number of residual cells at the end of induction or intensification therapy was the most important prognostic factor for prediction of RFS. Overall, our results show that immunophenotypical investigation of MRD strongly predicts outcome in patients with AML and that the number of residual leukemic cells correlates with multidrug resistance.

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