Acute myeloid leukemia with MYC rearrangement and JAK2 V617F mutation

Ohanian, Maro; Bueso‐Ramos, Carlos E.; Ok, Chi Young; Lin, Pei; Patel, Keyur P.; Alattar, Mona Lisa; Khoury, Joseph D.; Rozovski, Uri; Estrov, Zeev; Huh, Yang O.; Cortes, Jorge; Abruzzo, Lynne V.

doi:10.1016/j.cancergen.2015.06.004

Cited by 8 publications

(6 citation statements)

References 15 publications

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“…In our previous study of 22 patients with myeloid neoplasms with MYC amplification manifesting as dmins, MYC-immunopositivity was overexpressed, but varied between 15–90%, suggesting mechanisms beyond amplification contribute to MYC-immunopositivity [22]. Only one previously reported patient[24] in this analysis had t(8;14)(q24;q32); thus the prognostic impact of this abnormality in AML could not be assessed. AML with t(8;14) (q24;q32) is extremely rare.…”

Section: Discussionmentioning

confidence: 77%

“…In the few reports available in the literature, AML with t(8;14)(q24;q32) is associated with poor outcomes[24,59]. In two previously reported cases of AML with MYC rearrangement from our group, MYC-immunopositivity was only marginally increased[24] and in the present study, MYC rearrangement was not present by FISH in 8 tested cases of normal karyotype AML with variable MYC-immunopositivity (0-70%), suggesting that MYC rearrangement is not a driver of MYC-immunopositivity in AML. This observation highlights the fact the regulators of MYC protein expression are quite complex and future studies are needed to understand these processes, particularly since targeting MYC therapeutically in AML is becoming increasingly possible [15].…”

Section: Discussionmentioning

confidence: 99%

“…Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) analysis was performed on BM as previously described [22,24]. Molecular analysis for NPM1, CEBPA and FLT3 mutations was performed by using PCR-based assays.…”

Section: Methodsmentioning

confidence: 99%

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MYC protein expression is an important prognostic factor in acute myeloid leukemia

Ohanian

Rozovski

Kanagal‐Shamanna

et al. 2018

Leukemia & Lymphoma

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As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p = .028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p = .042), event-free survival (EFS) (14 versus 6 months; p = .048), and relapse-free survival (RFS) (25 versus 12 months; p = .024). The prognostic impact of MYC-immunopositivity was retained on multivariate analysis of OS, EFS, and RFS. We conclude that MYC immunopositivity is an important prognostic factor in patients with untreated AML, particularly those at higher risk for relapse.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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MYC protein expression is an important prognostic factor in acute myeloid leukemia

Ohanian

Rozovski

Kanagal‐Shamanna

et al. 2018

Leukemia & Lymphoma

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“…28 In contrast to lymphoid tumors, MYC rearrangement associated with myeloid neoplasms has been assessed less frequently. 29 In this study, FISH analysis using a MYC break-apart probe showed split signals (a pattern indicating MYC rearrangement) in 16/18 patients. In a previous study, 30 the authors studied the breakpoint on 8q24.2 in two patients (Cases #4 and #5) by using a series of FISH probes and found that the breakpoint was just distal to MYC, but was within the green signal of the MYC break-apart probe.…”

Section: Discussionmentioning

confidence: 46%

t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression

Tang

Wang

et al. 2019

The Journal of Molecular Diagnostics

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t(3;8)(q26.2;q24) is a rare recurrent cytogenetic abnormality that is associated with myeloid neoplasms. Of 20 patients with t(3;8)(q26.2,q24), 8 had therapy-related acute myeloid leukemia (AML), 3 therapy-related myelodysplastic syndrome, 4 blast phase of chronic myeloid leukemia, 1 relapsed AML, 1 AML transformed from chronic myelomonocytic leukemia, 1 blast phase of an unclassifiable myeloproliferative neoplasm, 1 de novo myelodysplastic syndrome, and 1 de novo AML. Nineteen patients presented with cytopenia. Multilineage dysplasia was observed in 16/18 patients, and megakaryocytes were markedly decreased in 11/20 patients. Blasts showed a primitive myeloid immunophenotype in 17 patients, negative for myeloperoxidasein in 14/17, and aberrant CD7 expression in 5/17 patients. Fluorescence in situ hybridization showed MECOM rearrangement in 18/19 and MYC in 16/18 patients. Myc was shown to be expressed in all 14 cases assessed. Gene mutation testing was performed in 14 patients, and 7 showed at least one mutation including ASXL1 (2/6), TET2 (2/6), SRSF2 (2/6), and NRAS (2/13). At last clinical follow-up, 18 patients died and 2 were alive with persistent disease, with a median survival of 6 months. The authors conclude that t(3;8)(q26.2;q24) often leads to MECOM and MYC rearrangement, occurs predominantly in therapy-related myeloid neoplasms or at disease progression, and shares some similarities with myeloid neoplasms associated with inv(3)/GATA2-MECOM. Patients with myeloid neoplasms associated with t(3;8)(q26.2;q24) have a dismal outcome.Had occupational exposure to methylenechloride and 1, 1, 1-trichloroethane.

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“… 3-5 Recently, there have been cases of JAK2 V617F mutation in some leukemic patients without a history of JAK2 V617F positive MPNs. 106 , 107 The results of these studies suggest that this mutation is not specific to JAK2 V617F positive MPNs and that it may also be seen in normal individuals and underlie malignancies. Furthermore, there are case reports that indicate the co-existence of JAK2 V617F positive MPNs and leukemia in a single patient.…”

Section: Markers’ Expression During Leukemic Transformation In Jakmentioning

confidence: 95%

Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance

et al. 2018

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Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common clinical outcomes of these disorders. Recent studies have shown that abnormality in frequency and function of blood cells manifested by an alteration in CD markers’ expression patterns play a key role in these complications. So, there may be a relationship between CD markers’ expressions and prognosis of JAK2V617F positive MPNs. Therefore, in this review, we have focused on these abnormalities from the perspective of changing expressions of CD markers and assessment of the relationship between these changes with prognosis of JAK2V617F positive MPNs. It can be stated that the abnormal expression of a large number of CD markers can be used as a prognostic biomarker for clinical outcomes including thrombohememorrhagic events, as well as autoimmune and leukemic transformation in JAK2V617F positive MPNs. Considering the possible role of CD markers’ expressions in JAK2V617F MPNs prognosis, further studies are needed to confirm the relationship between the expression of CD markers with prognosis to be able to find an appropriate therapeutic approach via targeting CD markers.

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Acute myeloid leukemia with MYC rearrangement and JAK2 V617F mutation

Cited by 8 publications

References 15 publications

MYC protein expression is an important prognostic factor in acute myeloid leukemia

MYC protein expression is an important prognostic factor in acute myeloid leukemia

t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression

Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance

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