A4

https://journals.lww.com/co-hematology/Abstract/2007/03000/Influence_of_new_molecular_prognostic_markers_in.5.aspx

Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances

Mrózek, Krzysztofa; Döhner, Hartmutb; Bloomfield, Clara Da

Current Opinion in Hematology: March 2007 - Volume 14 - Issue 2 - p 106–114

doi: 10.1097/MOH.0b013e32801684c7

Myeloid disease

Purpose of review Molecular study of cytogenetically normal acute myeloid leukemia is among the most active areas of leukemia research. Despite having the same normal karyotype, adults with de-novo cytogenetically normal acute myeloid leukemia who constitute the largest cytogenetic group of acute myeloid leukemia, are very diverse with respect to acquired gene mutations and gene expression changes. These genetic alterations affect clinical outcome and may assist in selection of proper treatment. Herein we critically summarize recent clinically relevant molecular genetic studies of cytogenetically normal acute myeloid leukemia.

Recent findings  NPM1 gene mutations causing aberrant cytoplasmic localization of nucleophosmin have been demonstrated to be the most frequent submicroscopic alterations in cytogenetically normal acute myeloid leukemia and to confer improved prognosis, especially in patients without a concomitant FLT3 gene internal tandem duplication. Overexpressed BAALC, ERG and MN1 genes and expression of breast cancer resistance protein have been shown to confer poor prognosis. A gene-expression signature previously suggested to separate cytogenetically normal acute myeloid leukemia patients into prognostic subgroups has been validated on a different microarray platform, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are still needed.

Summary The discovery of new prognostic markers has increased our understanding of leukemogenesis and may lead to improved prognostication and generation of novel risk-adapted therapies.

http://www.bloodjournal.org/content/127/1/53?sso-checked=true

An update of current treatments for adult acute myeloid leukemia

Hervé Dombret and Claude Gardin

Abstract

Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents.