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 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

 

Indicate if the entire panel is to be performed. If the patient is being treated for known abnormalities, indicate which probes should be used.

 

Indicate the subtype, as well as, which abnormalities need to be investigated from the following profile:

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

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

11p15.4 rearrangement, NUP98

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

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

+8, [M0-M7], D8Z2/MYC

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(3;5)(q25.32;q35.1), MLF1/NPM1

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

-5/5q-, D5S630/EGR1

-7/7q-, D7S486/D7Z1

13q-, D13S319/LAMP1

17p-, TP53/D17Z1

20q-, D20S108/20qter

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 NUP98 rearrangement is identified, reflex testing using the HOXA9/NUP98 probe set will be performed to identify a potential t(7;11)(p15;p15.4).

-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 this test is ordered and the laboratory is informed that the patient is on a 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 subtypes of AML have been recognized (termed AML-M0, M1, M2, M3, M4, M5, M6, and M7) based on the cell morphology and myeloid lineage involved.

 

In addition to morphology, several recurrent chromosomal abnormalities have been linked to specific subtypes of AML. The most common chromosome abnormalities associated with AML include t(8;21), t(15;17), inv(16), +8, t(6;9), t(8;16), t(1;22), t(9;22), t(3;5), and abnormalities of the MLL (KMT2A) gene at 11q23. The most common genes juxtaposed with MLL through translocation events in AML include AFF1- t(4;11), MLTT4- t(6;11), MLLT3- t(9;11), MLLT10- t(10;11), CREBBP- t(11;16), ELL- t(11;19p13.1), and MLLT1- t(11;19p13.3).

 

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-, +8, 13q-, 17p-, 20q-, t(1;3), and t(3;21). In combination, the multiple 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: eg, inv(16), MLL and NUP98 abnormalities.

 

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 this 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 FISH 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. International Agency for Research on Cancer (IARC): World Health Organization Classification of Tumour of Haematopoietic and Lymphoid Tissues. Fourth edition. Edited by SH Swerdlow, E Campo, NL Harris, et al. IARC Press, Lyon, France. Oxford University Press, 2008

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