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Test Catalog

Test ID: COGMF    
Acute Myeloid Leukemia (AML), Children's Oncology Group Enrollment Testing, FISH, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of pediatric bone marrow and peripheral blood specimens by fluorescence in situ hybridization (FISH) probe analysis for classic rearrangements and chromosomal copy number changes associated with acute myeloid leukemia (AML) in patients being considered for enrolment in Children's Oncology Group (COG) clinical trials and research protocols

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test is only performed on specimens from pediatric patients who are candidates for enrollment in Children's Oncology Group (COG) clinical trials and research protocols.

 

For diagnostic samples, all probes in the initial panel will be performed. The initial panel includes testing for the following abnormalities using the probes listed:

t(8;21), [M2], RUNX1T1/RUNX1

t(15;17), [M3], PML/RARA

11q23 rearrangement, [M0-M7], MLL (KMT2A)

inv(16), [M4, Eos], MYH11/CBFB

Based on the results from the initial panel, reflex testing may be performed to identify the following abnormalities:

t(6;9), [M2,M4], DEK/NUP214

inv(3) or t(3;3), [M1,2,4,6,7], RPN1/MECOM

t(8;16), [M4,M5], MYST3/CREBBP

t(1;22), [M7], RBM15/MKL1*

-5/5q-, D5S630/EGR1

-7/7q-, D7S486/D7Z1

17p-, TP53/D17Z1

t(9;22), BCR/ABL1

 *The RBM15/MKL1 probe set will only be used to test patients with a suspected or confirmed diagnosis of M7 or to confirm a t(1;22) identified by chromosome analysis.

 

-When a MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1/MLL, t(6;11)(q27;q23) MLLT4/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p13;q23) MLLT10/MLL, t(11;16)(q23;p13.3) MLL/CREBBP, t(11;19)(q23;p13.1) MLL/ELL, or t(11;19)(q23;p13.3) MLL/MLLT1.

-When 3 copies of MECOM are observed with no fusion with RPN1, reflex testing using the MECOM/RUNX1 probe set will be performed to identify a potential t(3;21)(q26.2;q22) rearrangement.

-When 3 copies of RPN1 are observed with no fusion with MECOM, reflex testing using the PRDM16/RPN1 probe set will be performed to identify a potential t(1;3)(p36;q21).

 

The following testing algorithm is recommended for patients with acute myeloid leukemia (AML):

-At diagnosis, AML FISH panel and/or conventional chromosome studies COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow should be performed. If there is limited specimen available, only the COGMF / Acute Myeloid Leukemia (AML), FISH, Children's Oncology Group Enrollment Testing, varies will be performed.-If this test is ordered and the laboratory is informed that the patient is not on a COG protocol, this test will be canceled and automatically reordered by the laboratory as AMLF / Acute Myeloid Leukemia (AML), FISH, Varies.

 

See Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up in Special Instructions

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Acute myeloid leukemia (AML) is one of the most common adult leukemias, with almost 10,000 new cases diagnosed per year. AML also comprises 15% of pediatric acute leukemia and accounts for the majority of infant (<1 year old) leukemia.

 

Several recurrent chromosomal abnormalities have been identified in AML. The most common chromosome abnormalities associated with AML include t(8;21), t(15;17), inv(16), and abnormalities of the MLL (KMT2A) gene at 11q23. The most common genes juxtaposed with MLL through translocation events in AML include MLTT4- t(6;11), MLLT3- t(9;11), MLLT10- t(10;11), and ELL- t(11;19p13.1).

 

AML can also evolve from myelodysplasia (MDS). Thus, the common chromosome abnormalities associated with MDS can also be identified in AML, which include: inv(3), -5/5q-, -7/7q-, and 17p. Overall, the recurrent chromosome abnormalities identified in patients with AML are observed in approximately 60% of diagnostic AML cases.

 

Conventional chromosome analysis is the gold standard for identification of the common, recurrent chromosome abnormalities in AML. However, some of the subtle rearrangements can be missed by karyotype, including inv(16) and MLL rearrangements.

 

Fluorescence in situ hybridization (FISH) analysis of nonproliferating (interphase) cells can be used to detect the common chromosome abnormalities observed in patients with AML. The abnormalities have diagnostic and prognostic relevance, and FISH testing can also be used to track response to therapy.

 

Metaphase FISH confirmation of classic translocations that are cryptic and not visually detectable by chromosome analysis (ie, t[12;21] associated with ETV6/RUNX1 fusion) is performed as required by Children's Oncology Group (COG) and is included as part of the electronic case submission by the Mayo Clinic Genomics Laboratory to COG for central review.

 

Additional cytogenetic techniques such as chromosomal microarray (CMAH / Chromosomal Microarray, Hematologic Disorders, Varies) may be helpful to resolve questions related to ploidy (hyperdiploid clone vs doubled hypodiploid clone) or to resolve certain clonal structural rearrangements such as the presence or absence of intrachromosomal amplification of chromosome 21 (iAMP21).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

 

Detection of an abnormal clone likely indicates a diagnosis of an acute myeloid leukemia of various subtypes.

 

The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the US Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.

 

Bone marrow is the preferred specimen type for this fluorescence in situ hybridization test. If bone marrow is not available, a blood specimen may be used if there are malignant cells in the blood specimen (as verified by a hematopathologist).

Supportive Data

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs were calculated based on the results of 25 normal specimens. For each probe set a series of chromosomally abnormal specimens were evaluated to confirm each probe set detected the abnormality it was designed to detect.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Grimwade D, Hills RK, Moorman AV, et al: Refinement of cytogenetics classification in acute myeloid leukemia: determination of prognostic significance or rare recurring chromosomal abnormalities among 5879 younger adult patients treated in the United Kingdom Research Council trials. Blood. 2010 Jul;116(3):354-365

2. Swerdlow SH, Campo E, Harris NL, et al. eds: International Agency for Research on Cancer (IARC): World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Oxford University Press; 2017

3. Manola KN: Cytogenetics of pediatric acute myeloid leukemia. Eur J Haematol. 2009;83(5):391-405

Special Instructions Library of PDFs including pertinent information and forms related to the test