Heterogeneity in refractory acute myeloid leukemia

Horibata, Sachi; Gui, Gege; Lack, Justin; DeStefano, Christin B.; Gottesman, Michael M.; Hourigan, Christopher S.

doi:10.1073/pnas.1902375116

Cited by 50 publications

(45 citation statements)

References 70 publications

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“…Recent reports 31,32 on use of idarubicin in adult AML indicate: (a) that an increased cumulative dose of idarubicin during consolidation can improve leukemia-free survival; and (b) comparing idarubicin to high dose daunorubicin during induction did not indicate significant differences in CR rate, relapse and survival. Heterogeneity in development of resistant cells as well as differential expression in key pathways has been suggested to involved in refractory AML 33,34 . Analysis of topo II α and β expression coupled with immunophenotype in AML cells from patients with disease that is resistant to anthracycline/cytarabine therapy might provide insights on biomarkers relevant to outcome.…”

Section: Discussionmentioning

confidence: 99%

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia

Michelson

McDonough²,

Willman

et al. 2020

Sci Rep

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Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase ii (topo ii) isoforms, topo ii α and topo iiβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo iiβ by RT-pcR and its relationship to immunophenotype (ip) and outcomes. treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo iiβ (p < 0.0001). In contrast to topo IIα, topo iiβ was significantly associated with blast percentage in marrow or blood (p = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.

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Section: Discussionmentioning

confidence: 99%

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia

Michelson

McDonough²,

Willman

et al. 2020

Sci Rep

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“…There is only one paper, evaluating the role of NLR in formulating the prognosis in acute leukemia patients. Mushtaq et al 116 explored the association of NLR, overall survival (OS) and response to treatment in patients with relapsed/refractory acute myeloid leukemia (RR-AML). 63 adults with RR-AML were included.…”

Section: Nlr and Lmr In Leukemiasmentioning

confidence: 99%

<p>The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review</p>

Stefaniuk¹,

Szymczyk²,

Podhorecka³

2020

CMAR

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Despite the presence of many hematological prognostic indexes, clinical course and overall survival are often highly variable even within the same patient subgroup. Recent studies suggest that simple, cost-effective, low-risk tests such as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) may be used to evaluate the prognosis. Their role has been well confirmed in diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL) and multiple myeloma (MM), but until now the prognostic significance of NLR and LMR in leukemias has not been widely reported. In this article, we analyze the literature data on prognostic value of NLR and LMR in haematological malignancies in the context of classic prognostic factors and clinical course.

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“…therapy may induce its own chemoresistance mechanism. While steady-state expression of ABC transporters is seen only in a subset of resistant AML cases, we found that dynamic upregulation of ABCB1 following daunorubicin exposure occurred in all fresh primary samples tested (39). Rapid adaptation to therapy may therefore represent a more common mechanism of resistance than previously appreciated, especially considering that the biopsies that provide primary material for research are seldom taken during treatment.…”

Section: Methodsmentioning

confidence: 68%

A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia

Williams

Amaral²,

Simeoni

et al. 2020

Journal of Clinical Investigation

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Heterogeneity in refractory acute myeloid leukemia

Abstract: Risk ratio = r=r 0 . r 0 = 0.28 (percentage of total Ref patients); r, probability of being in the refractory group given each category.Horibata et al.

Cited by 50 publications

References 70 publications

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia

<p>The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review</p>

A stress-responsive enhancer induces dynamic drug resistance in acute myeloid leukemia

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