scholarly journals Frequency, Characteristics and Prognostic Significance of RUNX1 mutations in Patients with Acute Myeloid Leukemia, Not Otherwise Specified

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3860-3860
Author(s):  
Mi-Hyun Bae ◽  
Young-Uk Cho ◽  
Bohyun Kim ◽  
Dong Hyun Lee ◽  
Seongsoo Jang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Hazard Ratio ◽  
Trisomy 13 ◽  
Transactivation Domain ◽  
Trisomy 8 ◽  
Not Otherwise Specified ◽  
Acute Myeloid

Abstract Background: Somatic mutations in RUNX1 gene have been identified in a substantial proportion of patients with de novo acute myeloid leukemia (AML). It is suggested as a new candidate molecular marker and, therefore, is suggested to be routinely performed at the diagnostic stage of AML. Despite its clinical importance, however, previous cohorts have been heterogeneous in terms of cytogenetic and molecular subtypes of AML. Here, the aim of this study was to evaluate the frequency, biologic characteristics, and prognostic significance of RUNX1 mutations focusing on patients with AML, not otherwise specified (NOS). Methods: Diagnostic samples from 202 patients with AML were analyzed for RUNX1 mutations. We excluded AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, and therapy-related AML because these entities have prognostic relevances of their own. RUNX1 mutations were detected using standard PCR techniques and direct sequencing. Results: RUNX1 mutations were found in 27 (13.4%) patients. The mutations were clustered in Runt homology domain (13, 48.1%) and transactivation domain (9, 33.3%). Frameshift mutations were most common (52.9%), followed by missense mutations (35.3%) and nonsense mutations (11.8%). As shown in Table 1, patients with RUNX1 mutations had a lower platelet count (P = 0.03), a higher rate of trisomy 8 (P = 0.02) and trisomy 13 (P = 0.039), and a trend toward older age (P = 0.063) than patients without mutations. Presence of RUNX1 mutations and NPM1 or CEBPA mutations were mutually exclusive. At the median follow-up of 12.1 months, RUNX1 mutations predicted for shorter overall survival (OS; P = 0.007) and relapse-free survival (RFS; P = 0.003). In the multivariate analysis, RUNX1 mutation was a significant marker for inferior OS (hazard ratio, 3.037; P = 0.014) and RFS (hazard ratio, 5.699; P = 0.001). Conclusion: The findings of our study further strengthen the previous data about RUNX1 mutations in AML. Furthermore, AML NOS with RUNX1 mutations is characterized by distinct biology and is associated with adverse clinical outcome. Our study supports the notion that RUNX1 mutational status would be integrated into diagnostic workup of AML, particularly for AML, NOS subgroup. Table 1. Clinical and biologic features of the cohort by RUNX1 mutations RUNX1 mutations P -value Mutated, n (%) Wild type, n (%) Number 27 (13.4) 175 (86.6) Male sex 17 (63.0) 94 (53.7) 0.489 Median age, years (range) 63 (14 - 80) 55 (1 - 83) 0.063 WBC count, ¡¿109/L (median, range) 7.9 (1.1 - 133.3) 14.0 (0.8 - 231.3) 0.636 Hemoglobin, g/dL (median, range) 8.6 (5.0 - 10.6) 8.8 (4.1 - 17.3) 0.376 Platelet count, ¡¿109/L (median, range) 35 (14 - 230) 59 (9 - 900) 0.03 Blood blasts, % (median, range) 29 (0 - 94) 38.5 (0 - 93) 0.312 FAB subtypes  M0 3 (11.1) 11 (6.3) 0.609  M1, M2 21 (77.8) 129 (73.7) 0.831  M4, M5 3 (11.1) 27 (15.4) 0.767  M6, M7 0 8 (4.6) 0.546 Cytogenetic abnormalities  Normal karyotype (%) 11 (40.7) 104 (59.4) 0.106  Trisomy 8 (%) 5 (18.5) 8 (4.6) 0.02  Trisomy 11 (%) 1 (3.7) 4 (2.3) 0.823  Trisomy 13 (%) 3 (11.1) 3 (1.7) 0.039  Trisomy 21 (%) 1 (3.7) 2 (1.1) 0.866 Distribution of other mutations  FLT3 -ITD 5 (18.5) 50 (28.6) 0.39  FLT3 -TKD 1 (3.7) 4 (2.3) 0.823  NPM1 0 55 (31.4) 0.002  CEBPA 0 17 (9.7) 0.187  MLL -PTD 1 (3.7) 14 (8.0) 0.691 Disclosures No relevant conflicts of interest to declare.

scholarly journals The possible significance of trisomy 8 in acute myeloid leukemia

2017 ◽  
Vol 5 (6) ◽  
pp. 2652 ◽  
Author(s):  
Salil N. Vaniawala ◽  
Monika V. Patel ◽  
Pratik D. Chavda ◽  
Shivangi H. Zaveri ◽  
Pankaj K. Gadhia
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chromosomal Aberrations ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Chromosomal Translocation ◽  
Banding Technique ◽  
Trisomy 8 ◽  
Increased Risk ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while  three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.

Prognostic Significance of Mutations In Isocitrate Dehydrogenase (IDH) Enzyme Isoforms 1 and 2 and Single Nucleotide Polymorphisms (SNP) In IDH1, In Patients with Acute Myeloid Leukemia Treated with High Dose Cytarabine and Idarubicin Induction

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2706-2706
Author(s):  
Farhad Ravandi ◽  
Keyur P. Patel ◽  
Rajyalakshmi Luthra ◽  
Stefan Faderl ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Normal Karyotype ◽  
High Dose ◽  
Single Nucleotide ◽  
Pre Treatment ◽  
Acute Myeloid

Abstract Abstract 2706 Background IDH1 and IDH2 gene mutations have been identified as novel, recurring molecular aberrations among patients with normal karyotype acute myeloid leukemia (AML). The potential impact of these mutations as well as an IDH1 single nucleotide polymorphism (SNP) on the outcome of the patients is being actively investigated. Materials and Methods Among 358 patients with AML treated from October 2004 to February 2010 on 4 consecutive protocols using high dose ara-C plus idarubicin induction therapy (IA alone, IA plus tipifarnib [IAT], IA plus sorafenib [IAS], and IA plus vorinostat [IAV]), pre-treatment samples were available for 170 patients [median age 53 years, (range, 17 – 73); 96% ≤ 65 years] for testing for IDH1R132, IDH2R172 and IDH2R140 mutations. All patients received an induction course of therapy followed by up to 5 reduced-dose consolidation cycles followed by maintenance therapy with T, S, or V for up to a year; patients treated with IA had no maintenance. We examined whether presence of mutations in either gene or the codon 105 SNP in IDH1 was associated with pre-treatment characteristics or outcome. We also sought whether treatment with any of the 4 regimens had an impact on the outcome of patients with IDH aberrations. Results Overall, IDH1 and IDH2 mutations were present in 12 (7%) and 24 (14%) patients, respectively, and IDH1G105 SNP in 24 (14%). Overall, 52 (30%) patients had IDH gene aberrations; 2 patients had concomitant IDH1R132 mutation and IDH1G105 SNP, 3 patients had IDH2R140 mutation and IDH1G105 SNP, 1 patient IDH2R172 mutation and IDH1G105 SNP, and 1 patient had IDH1R132 mutation, IDH1G105 SNP, and IDH2R140 mutation. There was a strong association with normal karyotype with 11 of 12 (92%) of IDH1 mutated, 18 of 24 (75%) of IDH2 mutated, and 18 of 24 (75%) of IDH1 SNP being diploid. There was no association between any of the aberrations and patient age, sex, therapy-related vs. de novo AML, presenting WBC, peripheral blood blasts, or FAB subtype. IDH1 mutation was associated with a higher presenting platelet count (median 99 vs. 50 × 109/L in IDH1 wild-type [WT], p<0.05) and IDH1 SNP with a higher platelet count (median 68 vs. 46 × 109/L in IDH1WT, p<0.04) and a lower bone marrow blast percentage (median 39% vs. 54% in IDH1WT, p<0.03). 12 of 52 patients with IDH aberrations also had FLT3-ITD compared to 22 of 128 patients with IDH-WT (p=NS). There was no association with achievement of complete response (CR), remission duration, overall and event-free survival and any the IDH aberrations. Furthermore, there was no association with a higher CR rate or survival among any of the 4 different regimens for the 52 patients with aberrant IDH gene. Conclusions IDH aberrations including mutations and SNP occur in about 30% of younger patients with AML, mostly with diploid karyotype. IDH1 mutations and SNP are associated with a higher presenting platelet count and SNP with lower bone marrow blasts. Using high-dose ara-C based induction regimens, we did not detect an association with outcome for any of the aberrations. Disclosures: No relevant conflicts of interest to declare.

The Prognostic Significance of Trisomy 8 in Patients With Acute Myeloid Leukemia

2002 ◽  
Vol 43 (3) ◽  
pp. 583-586 ◽  
Author(s):  
Michelle A. Elliott ◽  
Louis Letendre ◽  
Curtis A. Hanson ◽  
Ayalew Tefferi ◽  
Gordon W. Dewald
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Trisomy 8 ◽  
Acute Myeloid

scholarly journals EXTRAMEDULLARY INVOLVEMENT IN ACUTE MYELOID LEUKEMIA. A SINGLE CENTER TEN YEARS EXPERIENCE

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Luana Fianchi ◽  
Martina Quattrone ◽  
Marianna Criscuolo ◽  
Silvia Bellesi ◽  
Giulia Dragonetti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Best Supportive Care ◽  
Monocytic Leukemia ◽  
Trisomy 8 ◽  
Extramedullary Relapse ◽  
Incidence Risk ◽  
The Impact ◽  
Acute Myeloid

The incidence, risk factors and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia have not been established yet. This study analyzed the clinical and biological characteristics, the impact on prognosis and the cumulative incidence of EMI in a monocentric retrospective study. All consecutive adult pts with a diagnosis of AML observed in our institution between January 2010 and December 2017 were included into the analysis.Overall 346 AMLs were analyzed. The incidence of EMI was 11% (38 pts). The involved sites were: skin (66%), CNS (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most pts (91%) had only one site of EMI, while 9% had multiple sites affected at the same time. Twenty-four (55%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 9 pts (24%); 5 pts had EMI both at presentation and at relapse.EMI had a significantly higher frequency in pts with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), MLL rearrangements (p=0.001), trisomy 8 (p=0,02) and a specific cytofluorimetry pattern (CD117-, p= 0,03; CD56-/CD117-, p= 0,04; CD56+/CD117-, p= 0,04).An analysis regarding treatment, OS and DFS was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient received best supportive care and was consequently excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 pts), hypomethylating agent (5 pts) and low dose citarabine (1 pts); 8 pts (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). Complete remission (CR) rate after induction therapy was 22% with a median DFS of 7.4 months. Median OS of all 27 EMI pts was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI pts who undergone allo-HSCT than those (19 pts) who didn’t receive this procedure (16.7 vs 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for survival in our population (p<0,0001).This study confirms poor prognosis for EMI pts. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in the therapeutic approach of these patients, being associated with a better prognosis.

Genomic characteristics and prognostic significance of co‐mutated ASXL1 / SRSF2 acute myeloid leukemia

2021 ◽  
Author(s):  
Daniel R. Richardson ◽  
David M. Swoboda ◽  
Dominic T. Moore ◽  
Steven M. Johnson ◽  
Onyee Chan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Acute Myeloid

scholarly journals FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Naval Daver ◽  
Sangeetha Venugopal ◽  
Farhad Ravandi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Prognostic Significance ◽  
Treatment Algorithm ◽  
Molecular Testing ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Acute Myeloid

AbstractApproximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. Current guidelines recommend rapid molecular testing for FLT3mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3mut AML have improved outcomes in patients with FLT3mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s in R/R FLT3mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML.

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