TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: AMLF    
Acute Myeloid Leukemia (AML), FISH, Varies

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

Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with acute myeloid leukemia or other myeloid malignancies

 

Evaluating specimens in which standard cytogenetic analysis is unsuccessful

 

Identifying and tracking known chromosome abnormalities in patients with myeloid malignancies and tracking response to therapy

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

This test includes a charge for application of the first probe set (2 fluorescence in situ hybridization: FISH probes) and professional interpretation of results. Additional charges will be incurred for all reflex probes performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

 

The following algorithms are available in Special Instructions:

-Acute Leukemias of Ambiguous Lineage Testing Algorithm

-Acute Myeloid Leukemia: Testing Algorithm

-Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up

 

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).

-When 3 copies of RARA are observed with no fusion with PML, reflex testing using the 5'RARA/3'RARA rearrangement probe set will be performed to identify a potential variant translocation involving RARA; example: t(17;var)( q21;?).

-In the absence of BCR/ABL1 fusion, when an extra signal for ABL1 is identified, reflex testing will be performed using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement.

 

If the patient is being treated for known abnormalities, indicate which probes should be used.

 

If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGMF / Acute Myeloid Leukemia (AML), Children's Oncology Group Enrollment Testing, FISH, Varies.

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 diagnostic and prognostic chromosome abnormalities observed in patients with AML. When recurrent translocations or inversions are identified, FISH testing can also be used to track response to therapy.

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 hematopathology).

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 NK, et al: eds. International Agency for Research on Cancer (IARC): World Health Organization Classification of Tumour of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press, Oxford University Press; 2008

3. Dohner H, Estey E, Grimwade D, et al: Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447 doi:10.1182/blood-2016-08-733196

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