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


Advisory Information


This test is only performed on specimens from pediatric patients being considered for enrollment in a Children's Oncology Group (COG) protocol. For all other patients, order AMLF / Acute Myeloid Leukemia (AML), FISH, Varies.

 

For children in whom disease relapse or a secondary myeloid neoplasm is a concern and enrollment in a new COG protocol is being considered; order COGBM / Chromosome Analysis, Hematologic Disorders, Children’s Oncology Group Enrollment Testing, Bone Marrow.



Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


1. Provide a reason for referral with each specimen, as well as flow cytometry and/or a bone marrow pathology report and Children's Oncology Group (COG) protocol number. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

 2. If a child has received an opposite sex bone marrow transplant prior to specimen collection for this protocol, convey this information to the laboratory.



Specimen Required


Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Bone marrow

Container/Tube: Green top (sodium heparin)

Specimen Volume: 1 to 2 mL

Collection Instructions:

Invert several times to mix bone marrow.

 

Acceptable:

Specimen Type: Blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 6 mL

Collection Instructions:

Invert several times to mix blood.


Useful For

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

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
_PBCT Probe, +2 No, (Bill Only) No
_PADD Probe, +1 No, (Bill Only) No
_PB02 Probe, +2 No, (Bill Only) No
_PB03 Probe, +3 No, (Bill Only) No
_IL25 Interphases, <25 No, (Bill Only) No
_I099 Interphases, 25-99 No, (Bill Only) No
_I300 Interphases, >=100 No, (Bill Only) No

Testing Algorithm

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

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

COG, AML, FISH

Specimen Type

Varies

Specimen Minimum Volume

Blood: 2 mL
Bone Marrow: 1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Refrigerated 

Clinical Information

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

An interpretive report will be provided.

Interpretation

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.

Clinical Reference

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

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Results reported Monday through Friday, 8 a.m.-5 p.m.

Analytic Time

7 days

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

88271 x 2, 88291-DNA probe, each (first probe set), Interpretation and report

88271 x 2-DNA probe, each; each additional probe set (if appropriate)

88271-DNA probe, each; coverage for sets containing 3 probes (if appropriate)

88271 x 2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)

88271 x 3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)

88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)

88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)

88275-Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
COGMF COG, AML, FISH In Process

 

Result ID Test Result Name Result LOINC Value
602276 Result Summary 50397-9
602277 Interpretation 69965-2
602278 Result Table 93356-4
602279 Result 62356-1
GC013 Reason for Referral 42349-1
GC014 Specimen 31208-2
602281 Source 31208-2
602282 Method 85069-3
602283 Additional Information 48767-8
602284 Disclaimer 62364-5
602285 Released By 18771-6