Myelodysplastic Syndromes

Primary Author: South, Sarah T., PhD.

  • Key Points
  • Diagnosis
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

Cytogenetic Testing for Myelodysplastic Syndromes (MDS)

Cytogenetic studies play a key role in the evaluation of patients with MDS; study results are used to establish a diagnosis, stratify patients into prognostic groups, guide medical management, and monitor disease progression. Clonal abnormalities are observed in approximately 50% of cases evaluated by metaphase cytogenetic analysis and in up to 80% of cases evaluated by cytogenomic single nucleotide polymorphism (SNP) microarray.

Patients who may have clonal genetic abnormalities that can be detected by cytogenomic SNP microarray include normal karyotype, suboptimal (<20) normal metaphases, or failed metaphase chromosome study. Cytogenomic SNP microarray testing can detect copy-number alteration and copy-neutral loss of heterozygosity (LOH), which are often due to mutations and subsequent selection of mutant tumor-suppressor genes and oncogenes. Many copy-number alterations identified by cytogenomic SNP microarray may be monitored by FISH.

Conventional Cytogenetics (Karyotype) Fluorescence in situ Hybridization (FISH) Cytogenomic Microarray Testing
Suggested Use
Diagnosis, prognosis, and monitoring of minimal residual disease (MRD)

May increase diagnostic sensitivity in MDS if metaphase cytogenetic study is suboptimal (<20 normal metaphases) or fails

Use to clarify findings from an abnormal karyotype

Use to establish and/or monitor for abnormal clone

Complements conventional cytogenetic methods

Detects copy number alterations (loss/gain of DNA) and loss of heterozygosity (LOH)

Only method that can identify MDS-associated LOH (eg, uniparental disomies like UPD7q, UPD11q and UPD17p)

A more comprehensive analysis of myeloid-associated genomic alterations may be obtained through combined analysis of copy-number, loss of heterozygosity, and somatic mutations using cytogenomic microarray combined with next generation sequencing

Limitations

G-banded metaphase chromosome analysis has limited resolution

May fail to identify subtle abnormalities.

Cannot identify cryptic (sequence-level) alterations or LOH

Complex rearrangements or uncertainty of additional genomic material may require further clarification by molecular methods

Success rate dependent upon growth of tumor cells in culture

Standard MDS FISH panels are unlikely to increase diagnostic sensitivity when complete (20-cell) metaphase cytogenetic study is normal

Chromosome alterations outside FISH probe region are not detected

Cannot detect LOH

Microarray will detect only copy-number alterations and LOH

Microarray cannot detect balanced genomic rearrangements such as translocations, inversions, or balanced insertions, and may not detect low-level mosaicism (<15-20%)

ARUP Tests

Chromosome Analysis, Bone Marrow with Reflex to Genomic Microarray 2007130

Chromosome Analysis, Bone Marrow 2002292

Myelodysplastic Syndrome (MDS) Panel by FISH 2002709

Acute Myelogenous Leukemia (AML) with Myelodysplastic Syndrome (MDS), or Therapy-Related AML, by FISH 2002653

Cytogenomic SNP Microarray-Oncology  2006325

Cytogenomic Molecular Inversion Probe Array, FFPE Tissue – Oncology 2010229

Myeloid Malignancies Somatic Mutation and Copy Number Analysis Panel 2012182

 Cazzala M et al, 2011; Shih AH, 2011; Simons A, 2012;  Tiu RV, 2011; Coleman JF, 2011

Indications for Testing

  • Abnormal CBC or peripheral smear in the absence of obvious etiology – cytopenias and dysplastic cells in peripheral smear are most common

Criteria for Diagnosis

  • MDS – International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) (Mufti, 2008)
    • Stable cytopenia for >6 months
      • Only 2 months required if accompanied by specific karyotype or bilineage dysplasia
    • Exclusion of other potential disorders as a primary reason for dysplasia or cytopenia
    • At least one MDS-related (decisive) criterion
      • Unequivocal dysplasia (≥10% in ≥1 of the 3 major bone marrow lineages)
      • Blast cell count of 5-19%
      • Specific MDS-associated karyotype [eg, del(5q), del(20q), +8, -7/del(7q)]
    • Co-criteria help confirm the diagnosis
      • Bone marrow histology and immunohistochemistry to detect fibrosis, dysplastic megakaryocytes, atypical localization of immature progenitors
      • Flow cytometric analysis to identify abnormal myeloid antigen patterns, abnormal CD34 expression in blasts
      • Molecular markers to detect myeloid clonality
  • Presumptive MDS – this diagnosis is for individuals with refractory cytopenia(s) who lack unequivocal dysplasia if specific cytogenetic abnormalities are detected
  • AML with myelodysplasia-related changes
    • >20% blood or marrow blasts AND previous history of MDS or MDS-related cytogenetic abnormality OR multilineage dysplasia
      • Dysplasia in at least 50% of cells in 2 or more hematopoietic lineages
    • Absence of cytogenetic abnormalities described in AML with recurrent genetic abnormalities
    • No history of prior cytotoxic therapy for an unrelated disease
  • Therapy-related myeloid neoplasms (t-MDS, t-MDS/MPN, or t-AML)
    • Myeloid neoplasms (excluding MPNs) that arise as a consequence of cytotoxic or radiation therapy
    • May be subdivided by blast count but behave as a single biologic disease

Histology

  • Classification based on peripheral smear, bone marrow histology, and cytogenetic testing
    • Bone marrow biopsy – diagnosis almost exclusively made using marrow appearance
      • Criteria – dysplasia in ≥10% of myeloid lineage cells
    • Flow cytometry
      • Changes not specific for MDS – may be most useful in ruling out other neoplasms associated with cytopenias
      • Absence of  flow cytometric abnormalities does not exclude MDS
    • Cytogenetic testing – see Key Points section
    • Immunohistochemistry – CD117 (c-Kit); CD34 (QBEnd/10); myeloperoxidase (MPO) to identify abnormal localization of immature precursors and increased blasts

Prognosis

  • Most accurately defined by cytogenetic testing, FISH, and cytogenetic SNP microarray/next generation sequencing (see Key Points section)
  • Influenced by karyotype, % blasts, number of cytopenias present, and somatic mutations
  • Newest prognostication from WHO classification-based scoring system incorporates transfusion burden
    • Poor prognosis with refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-t)
      • Median survival 5-12 months
      • Disease transforms to AML in 40-50%
    • Better prognosis with refractory anemia (RA) or refractory anemia with ring sideroblasts (RARS)
      • Median survival 3-6 years
      • Disease transforms to AML in 5-15%

Differential Diagnosis

  • Cytopenias
    • Pancytopenia
      • Medication/toxin exposure
      • Bone marrow failure – aplastic anemia
      • Hemophagocytic syndrome
      • Acute leukemias – AML, ALL
      • Alcohol abuse
      • Infections
      • Severe nutritional deficiency
      • Bone marrow infiltration by malignancy
  • Isolated anemia
  • Isolated neutropenia
    • Acute leukemias (AML, ALL)
    • Medications (eg, sulfonamides, ganciclovir)
    • HIV
    • Hypersplenism
    • Familial cyclic neutropenia
    • Antineutrophil antibody syndromes
  • Isolated thrombocytopenia
    • Idiopathic thrombocytopenic purpura
    • Hypersplenism
  • Dyserythropoiesis
  • Other

Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies characterized by ineffective hematopoiesis, cytopenia, unilineage, or multilineage dysplasia with increased susceptibility to acute myeloid leukemia.

Epidemiology

  • Incidence
    • 4-5/100,000 in the general population (NCCN, 2015)
    • 30-56/100,000 in the elderly population (≥70 years) (NCCN, 2015)
  • Age – median is 65-70
  • Sex – M>F

Classification

  • Therapy-related neoplasm (WHO, 2008)
  • AML or MDS in individual exposed to cytotoxic agents

Risk Factors

  • Older age
  • Occupational exposures
    • Benzene-containing products
    • Pesticides
    • Organic solvents
    • Heavy metals (lead, arsenic)
  • Drug exposures
    • Alkylating agents, purine analogues, topoisomerase inhibitors
    • Azathioprine
    • Mycophenolate
  • Radiation
  • Genetic
    • Down syndrome
    • Fanconi anemia
    • Familial myelodysplasia
    • Diamond-Blackfan syndrome
    • Neurofibromatosis

Pathophysiology

  • Clonal expansion of the multipotential hematopoietic cell
  • Primary mechanism is defective maturation of marrow cells coupled with premature cell death

Clinical Presentation

  • MDS
    • May be asymptomatic
      • Disease is generally indolent, with blood counts remaining relatively stable over months or longer
    • Most common symptoms
      • Pallor, weakness, exertional dyspnea – secondary to anemia
      • Recurrent infections – secondary to neutropenia
      • Bleeding/bruising – secondary to thrombocytopenia
    • May have concomitant immune disorders (eg, relapsing polychondritis, vasculitis)
    • Complications
      • 25-30% progress to AML; incidence depends on MDS subtype
        • Lower response rate to standard therapy for patients >65 years with de novo AML
      • Death from complications of cytopenia (neutropenia in particular)
  • AML with myelodysplasia-related change
    • Elderly individuals predominate
    • Represents 25-30% of AML cases
    • Generally presents with pancytopenia
    • Chromosome abnormalities are similar to those found in MDS unrelated to cytotoxic agents
      • Often involve gain or loss of major segments of specific chromosomes with complex karyotypes
  • Treatment-related myeloid neoplasms
    • Late complication of cytotoxic or radiation therapy
      • Rate of development does not differ between those with a hematologic versus solid malignancy
    • Accounts for 10-20% of all AML, MDS, and MDS/myeloproliferative neoplasms (MPN)
    • 90% have clonal chromosomal abnormality
      • Often complex
      • Similar to those observed in AML with myelodysplasia-related change
    • Disease differs based on type of therapy (alkylating agent/radiation versus topoisomerase II)
      • Individual may have received both therapies at some point during an illness, meaning either presentation can occur
      • t-MDS/t-AML arising after alkylating agent and/or radiation therapy
        • 80–85% of treatment-related myeloid neoplasms
        • Latency period 3-7 years (median 5 years)
        • Initial presentation – MDS with trilineage dysplasia
        • Cytogenetics (most common)
          • Abnormalities of chromosomes 5, 7, or complex karyotypes
      • t-AML/t-MDS arising after topoisomerase II inhibitor therapy
        • ~15% of treatment-related myeloid neoplasms
        • Latency period 2-3 years
        • Initial presentation – AML (typically no antecedent MDS)
        • Cytogenetics
          • Balanced translocations
          • MLL rearrangements
          • t(15;17)
          • inv (16)

Clinical Background

Epidemiology

  • Incidence – rare; 1-4/million (NCCN, 2015)
  • Age – 6.8 years median

Risk Factors

  • Strongly associated with congenital disorders – evident in at least 50% of cases
    • Congenital disorders include
      • Down syndrome
      • Fanconi syndrome
      • Trisomy 8
      • Diamond-Blackfan anemia
      • Neurofibromatosis type 1
      • Bloom syndrome
      • Noonan syndrome
      • Congenital neutropenia (Kostmann syndrome)
      • Shwachman-Diamond syndrome
      • Dubowitz syndrome
  • Prior exposure to radiation or chemotherapy

Classification

  • Patients with 2-19% blasts in peripheral blood and/or 5-19% blasts in bone marrow may be classified using the adult schema provisional – excludes patients with Down syndrome
  • Additional pediatric entity of refractory cytopenia of childhood is recognized
    • <2% blasts in peripheral blood and <5% blasts in bone marrow
    • Bilineage dysplasia

Clinical Presentation

  • May be asymptomatic
  • Most common symptoms
    • Pallor, weakness, exertional dyspnea – secondary to anemia
    • Hepatomegaly/splenomegaly
    • Arthralgias

Diagnosis

  • Refer to Diagnosis and Key Points section

Differential Diagnosis

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Chromosome Analysis, Bone Marrow with Reflex to Genomic Microarray 2007130
Method: Giemsa Band/Genomic Microarray (Oligo-SNP array)

Limitations 

Cytogenomic SNP microarray will detect only copy-number alterations and LOH

This technology cannot detect balanced genomic rearrangements such as translocations, inversions, or balanced insertions and may not detect low-level mosaicism (<15-20%)

Chromosome Analysis, Bone Marrow 2002292
Method: Giemsa Band

Limitations 

This technology cannot detect balanced genomic rearrangements such as translocations, inversions, or balanced insertions and may not detect low-level mosaicism (<15-20%)

Chromosome FISH, Interphase 2002298
Method: Fluorescence in situ Hybridization

Limitations 

FISH analysis is a targeted molecular cytogenetic method and chromosome alterations outside probe region are not detected

Limit of detection is probe dependent; approximately 1-5% in interphase nuclei

Myelodysplastic Syndrome (MDS) Panel by FISH 2002709
Method: Fluorescence in situ Hybridization

Limitations 

Panel detects only the specific aberrations targeted by the probes

Limit of detection is probe dependent; approximately 1-5% in interphase nuclei

Cytogenomic SNP Microarray - Oncology 2006325
Method: Genomic Microarray (Oligo-SNP Array)

Limitations 

Low-level mosaicism (<15-20%) may not be detected

May not be appropriate for individuals with expected lower levels of malignant cells

FFPE specimens must contain a region with ≥50% tumor

Not recommended for minimal residual disease

Does not detect

  • Balanced rearrangements; FISH should be used to evaluate specific balanced rearrangements according to indication
  • Base pair mutations and very small deletions/duplications
  • Imbalances of the mitochondrial genome
  • Positional information for chromosome rearrangements
  • Low-level clones

Acute Myelogenous Leukemia (AML) with Myelodysplastic Syndrome (MDS) or Therapy-Related AML, by FISH 2002653
Method: Fluorescence in situ Hybridization

Limitations 

Limit of detection is probe dependent – ~1-5% in interphase nuclei

MLL gene at 11q23 has multiple translocation partners which are not identified by this test

Panel detects only the specific aberrations targeted by the probes

Myeloid Malignancies Somatic Mutation and Copy Number Analysis Panel 2012182
Method: Massively Parallel Sequencing/Genomic Microarray (Oligo-SNP Array)

Limitations 

Mutations may be present below the limit of detection

Not intended to detect minimal residual disease

Myeloid Malignancies Mutation Panel by Next Generation Sequencing 2011117
Method: Massively Parallel Sequencing

Limitations 

Mutations may not be present below the limit of detection

Not intended to detect MRD

Cytogenomic Molecular Inversion Probe Array, FFPE Tissue - Oncology 2010229
Method: Molecular Inversion Probe Array

Limitations 

Low-level mosaicism (<15-20%) may not be detected

May not be appropriate for individuals with expected lower levels of malignant cells

FFPE specimens must contain a region with ≥50% tumor

Not recommended for minimal residual disease

Does not detect

  • Balanced rearrangements; FISH should be used to evaluate specific balanced rearrangements according to indication
  • Base pair mutations and very small deletions/duplications
  • Imbalances of the mitochondrial genome
  • Positional information for chromosome rearrangements
  • Low-level clones

PDGFRB FISH for Gleevec Eligibility in Myelodysplastic Syndrome/Myeloproliferative Disease (MDS/MPD) 2012147
Method: Fluorescence in situ Hybridization

CD117 (c-Kit) by Immunohistochemistry 2003806
Method: Immunohistochemistry

CD34, QBEnd/10 by Immunohistochemistry 2003556
Method: Immunohistochemistry

Myeloperoxidase (MPO) by Immunohistochemistry 2004014
Method: Immunohistochemistry

Guidelines

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM M, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012; 120(12): 2454-65. PubMed

Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, Porta MG Della, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, van de Loosdrecht AA, de Witte T, Cazzola M, European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013; 122(17): 2943-64. PubMed

Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, Cazzola M, Fenaux P, Germing U, Hellström-Lindberg E, Jinnai I, Manabe A, Matsuda A, Niemeyer CM, Sanz G, Tomonaga M, Vallespi T, Yoshimi A, International Working Group on Morphology of Myelodysplastic Syndrome. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica. 2008; 93(11): 1712-7. PubMed

NCCN Clinical Practice Guidelines in Oncology, Myelodysplastic Syndrome. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jan 2016]

Protocol for the Examination of Specimens From Patients With Hematopoietic Neoplasms Involving the Bone Marrow. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jun 2012. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di Maio M, Finelli C, Locatelli F, Marchetti M, Morra E, Musto P, Visani G, Tura S, Italian Society of Hematology. Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res. 2010; 34(12): 1576-88. PubMed

Valent P, Horny H, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb H, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstöcker M, Rüter B, Sperr WR, Stauder R, Wells DA. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: Consensus statements and report from a working conference. Leuk Res. 2007; 31(6): 727-36. PubMed

van de Loosdrecht AA, Ireland R, Kern W, Porta MG Della, Alhan C, Balleisen JSebastian, Bettelheim P, Bowen DT, Burbury K, Eidenschink L, Cazzola M, Chu SS C, Cullen M, Cutler JA, Dräger AM, Feuillard J, Fenaux P, Font P, Germing U, Haase D, Hellström-Lindberg E, Johansson U, Kordasti S, Loken MR, Malcovati L, Marvelde JG te, Matarraz S, Milne T, Moshaver B, Mufti GJ, Nikolova V, Ogata K, Oelschlaegel U, Orfao A, Ossenkoppele GJ, Porwit A, Platzbecker U, Preijers F, Psarra K, Richards SJ, Subirá D, Seymour JF, Tindell V, Vallespi T, Valent P, van der Velden VH J, Wells DA, de Witte TM, Zettl F, Béné MC, Westers TM. Rationale for the clinical application of flow cytometry in patients with myelodysplastic syndromes: position paper of an International Consortium and the European LeukemiaNet Working Group. Leuk Lymphoma. 2013; 54(3): 472-5. PubMed

General References

Adès L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014; 383(9936): 2239-52. PubMed

Barzi A, Sekeres MA. Myelodysplastic syndromes: a practical approach to diagnosis and treatment. Cleve Clin J Med. 2010; 77(1): 37-44. PubMed

Coleman JF, Theil KS, Tubbs RR, Cook JR. Diagnostic yield of bone marrow and peripheral blood FISH panel testing in clinically suspected myelodysplastic syndromes and/or acute myeloid leukemia: a prospective analysis of 433 cases. Am J Clin Pathol. 2011; 135(6): 915-20. PubMed

Daver N, Strati P, Jabbour E, Kadia T, Luthra R, Wang S, Patel K, Ravandi F, Cortes J, Dong XQin, Kantarjian H, Garcia-Manero G. FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia. Am J Hematol. 2013; 88(1): 56-9. PubMed

Elghetany T. Myelodysplastic syndromes in children: a critical review of issues in the diagnosis and classification of 887 cases from 13 published series. Arch Pathol Lab Med. 2007; 131(7): 1110-6. PubMed

Gangat N, Patnaik MM, Begna K, Kourelis T, Al-Kali A, Elliott MA, Hogan WJ, Letendre L, Litzow MR, Knudson RA, Ketterling RP, Hodnefield JM, Hanson CA, Pardanani AD, Tefferi A. Primary Myelodysplastic Syndromes: The Mayo Clinic Experience With 1000 Patients. Mayo Clin Proc. 2015; 90(12): 1623-38. PubMed

Garcia-Manero G. Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014; 89(1): 97-108. PubMed

Greenberg PL. Molecular and genetic features of myelodysplastic syndromes. Int J Lab Hematol. 2012; 34(3): 215-22. PubMed

Meers S. The myelodysplastic syndromes: the era of understanding. Eur J Haematol. 2015; 94(5): 379-90. PubMed

Naeem R. Cytogenetics of Hematologic Neoplasms. In Gersen SL, Keagle MB. The Principles of Clinical Cytogenetics, 3rd ed. New York: Springer New York, 2013.

Porta MGiovanni D, Lanza F, Del Vecchio L, Italian Society of Cytometry (GIC). Flow cytometry immunophenotyping for the evaluation of bone marrow dysplasia. Cytometry B Clin Cytom. 2011; 80(4): 201-11. PubMed

Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, Fanelli T, Bosi A, Vannucchi AM, Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014; 123(10): 1552-5. PubMed

Schlegelberger B, Göhring G, Thol F, Heuser M. Update on cytogenetic and molecular changes in myelodysplastic syndromes. Leuk Lymphoma. 2012; 53(4): 525-36. PubMed

Simons A, Sikkema-Raddatz B, de Leeuw N, Konrad NClaudia, Hastings RJ, Schoumans J. Genome-wide arrays in routine diagnostics of hematological malignancies. Hum Mutat. 2012; 33(6): 941-8. PubMed

Steensma DP. Myelodysplastic Syndromes: Diagnosis and Treatment. Mayo Clin Proc. 2015; 90(7): 969-83. PubMed

Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Harald S, Thiele J, Vardiman J. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: International Agency for Research on Cancer, 2008.

Tiu RV, Gondek LP, O'Keefe CL, Elson P, Huh J, Mohamedali A, Kulasekararaj A, Advani AS, Paquette R, List AF, Sekeres MA, McDevitt MA, Mufti GJ, Maciejewski JP. Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. Blood. 2011; 117(17): 4552-60. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Dunphy CH, O'Malley DP, Perkins SL, Chang C. Analysis of immunohistochemical markers in bone marrow sections to evaluate for myelodysplastic syndromes and acute myeloid leukemias. Appl Immunohistochem Mol Morphol. 2007; 15(2): 154-9. PubMed

Matynia AP, Szankasi P, Shen W, Kelley TW. Molecular genetic biomarkers in myeloid malignancies Arch Pathol Lab Med. 2015; 139(5): 594-601. PubMed

Medical Reviewers

Last Update: August 2016