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1.
Blood. 2017 Jul 27;130(4):410-423. doi: 10.1182/blood-2017-02-734541. Epub 2017 Jun 9.

Diagnosis and classification of hematologic malignancies on the basis of genetics.

Author information

1
Human Oncology and Pathogenesis Program, Department of Medicine.
2
Department of Pathology, and.
3
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Abstract

Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1- MPNs, which are largely defined by mutations in JAK2, CALR, or MPL In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63 Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells.

PMID:
28600336
PMCID:
PMC5533199
DOI:
10.1182/blood-2017-02-734541
[Indexed for MEDLINE]
Free PMC Article
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2.
Blood. 2017 Jul 27;130(4):424-432. doi: 10.1182/blood-2017-02-735290. Epub 2017 Jun 9.

Genetic predisposition to hematologic malignancies: management and surveillance.

Author information

1
Section of Hematology/Oncology, The University of Chicago Comprehensive Cancer Center, and.
2
Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL; and.
3
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA.

Abstract

As individuals with germ line predisposition to hematologic malignancies are diagnosed with increasing frequency, the need for clinical surveillance has become apparent. Unfortunately, few prospective data are available, so recommendations are based on collective experience and expert consensus. There is general agreement to advocate for expert consultation or referral of patients to centers with expertise in these syndromes, since presentations and disease progression can be subtle, and treatment strategies must be tailored. Here, we summarize and integrate expert consensus recommendations and medical management considerations for the patient newly diagnosed with a leukemia predisposition disorder. Indications to consider additional studies and referral for allogeneic stem cell transplantation are also discussed.

PMID:
28600339
PMCID:
PMC5533201
DOI:
10.1182/blood-2017-02-735290
[Indexed for MEDLINE]
Free PMC Article
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3.
Blood. 2017 Jul 27;130(4):433-439. doi: 10.1182/blood-2017-03-734533. Epub 2017 Jun 9.

The relative utilities of genome-wide, gene panel, and individual gene sequencing in clinical practice.

Kuo FC1,2,3, Mar BG2,4,5, Lindsley RC6,7, Lindeman NI1,2,3.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
2
Dana-Farber Cancer Institute, Boston, MA.
3
Department of Pathology, Harvard Medical School, Boston, MA.
4
Department of Pediatric Oncology, Boston Children's Hospital, Boston, MA.
5
Department of Pediatrics, Harvard Medical School, Boston, MA.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; and.
7
Department of Medicine, Harvard Medical School.

Abstract

Advances in technology that have transpired over the past 2 decades have enabled the analysis of cancer samples for genomic alterations to understand their biologic function and to translate that knowledge into clinical practice. With the power to analyze entire genomes in a clinically relevant time frame and with manageable costs comes the question of whether we ought to and when. This review focuses on the relative merits of 3 approaches to molecular diagnostics in hematologic malignancies: indication-specific single gene assays, gene panel assays that test for genes selected for their roles in cancer, and genome-wide assays that broadly analyze the tumor exomes or genomes. After addressing these in general terms, we review specific use cases in myeloid and lymphoid malignancies to highlight the utility of single gene testing and/or larger panels.

PMID:
28600338
PMCID:
PMC5813726
DOI:
10.1182/blood-2017-03-734533
[Indexed for MEDLINE]
Free PMC Article
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4.
Blood. 2017 Jul 27;130(4):440-452. doi: 10.1182/blood-2017-03-735639. Epub 2017 Jun 9.

High-throughput sequencing for noninvasive disease detection in hematologic malignancies.

Scherer F1,2, Kurtz DM1,2,3, Diehn M1,4,5, Alizadeh AA1,2,4,5.

Author information

1
Division of Oncology and.
2
Division of Hematology, Department of Medicine, Stanford University, Stanford, CA; and.
3
Department of Bioengineering, Department of Radiation Oncology.
4
Institute for Stem Cell Biology and Regenerative Medicine, and.
5
Stanford Cancer Institute, Stanford University, Stanford, CA.

Abstract

Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient. In other cancer types, CTCs are generally rare and noninvasive molecular detection relies on circulating tumor DNA (ctDNA) shed from tumor deposits into circulation. The ability to precisely detect and quantify CTCs and ctDNA could minimize invasive procedures and improve prediction of clinical outcomes. Technical advances in MRD detection methods in recent years have led to reduced costs and increased sensitivity, specificity, and applicability. Among currently available tests, high-throughput sequencing (HTS)-based approaches are increasingly attractive for noninvasive molecular testing. HTS-based methods can simultaneously identify multiple genetic markers with high sensitivity and specificity without individual optimization. In this review, we present an overview of techniques used for noninvasive molecular disease detection in selected myeloid and lymphoid neoplasms, with a focus on the current and future role of HTS-based assays.

PMID:
28600337
PMCID:
PMC5881609
DOI:
10.1182/blood-2017-03-735639
[Indexed for MEDLINE]
Free PMC Article
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