Detecting a neoplastic clone associated with recurrent chromosome abnormalities seen in adult patients with acute myeloid leukemia (AML) or other myeloid malignancies
An adjunct to conventional chromosome studies in patients with AML
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
This test should not be used to screen for residual AML.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AMLAB | Probe, Each Additional (AMLAF) | No, (Bill Only) | No |
This test includes a charge for the probe application, analysis, and professional interpretation of results for 4 probe sets (8 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The initial panel includes testing for the following abnormalities using the probes listed:
-inv(16), [M4, Eos], MYH11/CBFB
-t(8;21), [M2], RUNX1T1/RUNX1
-t(15;17), [M3], PML/RARA
-11q23 rearrangement, [M0-M7], MLL (KMT2A)
Based on the results from the initial panel, if testing was ordered concurrently with a chromosomal study (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow or CHRHB / Chromosome Analysis, Hematologic Disorders, Blood), testing will be held pending the results of the chromosome test. If the chromosome results are complete and informative, only appropriate secondary FISH probes will be selected and performed. If testing was NOT ordered concurrently with a chromosomal study each of the secondary probes will be performed. The secondary panel includes testing for the following abnormalities using the probes listed:
-t(6;9), [M2,M4], DEK/NUP214
-inv(3) or t(3;3), [M1,2,4,6,7], RPN1/MECOM
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/D7S486
-17p-, TP53/D17Z1
-t(9;22), ABL1/BCR
When an MLL (KMT2A) rearrangement is identified, appropriate 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(AFDN)/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p12;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. In the event an 11q23 translocation is identified by conventional chromosome analysis, only the targeted MLL reflex probe will be performed if applicable.
In the absence of RPN1/MECOM fusion, when an extra RPN1 signal is identified, reflex testing using the PRDM16/RPN1 probe set will be considered at the laboratory’s discretion to identify a potential t(1;3)(p36;q21). Laboratory discretion may be influenced by available karyotype results.
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing may be performed at the laboratory’s discretion using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement. Laboratory discretion may be influenced by available karyotype results.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using the 5'RARA/3'RARA rearrangement probe set may be performed at the laboratory’s discretion to identify a potential variant translocation involving RARA. example: t(17;var)(q21;?). Laboratory discretion may be influenced by available karyotype results.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal is identified, reflex testing may be performed at the laboratory’s discretion using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement. Laboratory discretion may be influenced by available karyotype results.
The following algorithms are available:
Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
Fluorescence In Situ Hybridization (FISH)
-5 (monosomy 5)
-7 (monosomy 7)
17p- (17p deletion) or TP53
5q- (5q deletion)
7q- (7q deletion)
Acute Promyelocytic Leukemia (APL) or RARA
AML-M0
AML-M1
AML-M2
AML-M3
AML-M4
AML-M4eo
AML-M5
AML-M7
inv(16) - inv(16) - MYH11/CBFB
inv(3) - inv(3) - RPN1/MECOM or RPN1/EVI
MLL or KMT2A (11q23) rearrangement
t(1;3)(p36.3;q21.3) - PRDM16/RPN1
t(10;11)(p13;q23) - MLLT10/MLL or AF10/MLL
t(11;16)(q23;p13.3) - MLL/CREBBP
t(11;19)(q23;p13.1) - MLL/ELL
t(11;19)(q23;p13.3) - MLL/MLLT1 or MLL/ENL
t(15;17)(q24.1;q21) - PML/RARA
t(16;16)(p13.1;q22) - MYH11/CBFB
t(3;21)(q26.2;q22) - MECOM/RUNX1or EVI1/AML1
t(3;3)(q21.3;q26.2) - RPN1/MECOM or RPN1/EVI1
t(4;11)(q21;q23) - AFF1/MLL or AF4/MLL
t(6;11)(q27;q23) - MLLT4/MLL or AF6/MLL
t(6;9)(p23;q34) - DEK/NUP214 or DEK/CAN
t(8;21)(q22;q22) - RUNX1T1/RUNX1 or ETO/AML1
t(9;11)(p22;q23) - MLLT3/MLL or AF9/MLL
t(9;22)(q34;q11.2) - BCR/ABL1
This test includes a charge for the probe application, analysis, and professional interpretation of results for 4 probe sets (8 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The initial panel includes testing for the following abnormalities using the probes listed:
-inv(16), [M4, Eos], MYH11/CBFB
-t(8;21), [M2], RUNX1T1/RUNX1
-t(15;17), [M3], PML/RARA
-11q23 rearrangement, [M0-M7], MLL (KMT2A)
Based on the results from the initial panel, if testing was ordered concurrently with a chromosomal study (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow or CHRHB / Chromosome Analysis, Hematologic Disorders, Blood), testing will be held pending the results of the chromosome test. If the chromosome results are complete and informative, only appropriate secondary FISH probes will be selected and performed. If testing was NOT ordered concurrently with a chromosomal study each of the secondary probes will be performed. The secondary panel includes testing for the following abnormalities using the probes listed:
-t(6;9), [M2,M4], DEK/NUP214
-inv(3) or t(3;3), [M1,2,4,6,7], RPN1/MECOM
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/D7S486
-17p-, TP53/D17Z1
-t(9;22), ABL1/BCR
When an MLL (KMT2A) rearrangement is identified, appropriate 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(AFDN)/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p12;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. In the event an 11q23 translocation is identified by conventional chromosome analysis, only the targeted MLL reflex probe will be performed if applicable.
In the absence of RPN1/MECOM fusion, when an extra RPN1 signal is identified, reflex testing using the PRDM16/RPN1 probe set will be considered at the laboratory’s discretion to identify a potential t(1;3)(p36;q21). Laboratory discretion may be influenced by available karyotype results.
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing may be performed at the laboratory’s discretion using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement. Laboratory discretion may be influenced by available karyotype results.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using the 5'RARA/3'RARA rearrangement probe set may be performed at the laboratory’s discretion to identify a potential variant translocation involving RARA. example: t(17;var)(q21;?). Laboratory discretion may be influenced by available karyotype results.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal is identified, reflex testing may be performed at the laboratory’s discretion using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement. Laboratory discretion may be influenced by available karyotype results.
The following algorithms are available:
Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
Varies
This test is only performed on specimens from patients with acute myeloid leukemia (AML) who are 31 years of age or older.
This test is intended for instances when the entire AML fluorescence in situ hybridization (FISH) panel is needed for an adult patient.
-If this test is ordered on a patient 30 years of age or younger, this test will be canceled and automatically reordered by the laboratory as AMLPF / Acute Myeloid Leukemia (AML), FISH, Pediatric, Varies.
- 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.
This test should not be used to screen for residual acute myeloid leukemia (AML). If the patient is being treated for known abnormalities or if limited AML FISH probes are preferred, order AMLMF / Acute Myeloid Leukemia (AML), Specified FISH, Varies and request specific probes or abnormalities.
At follow-up, targeted AML FISH probes can be evaluated based on the specific abnormalities identified in the diagnostic study. Order AMLMF and request specific probes or abnormalities.
For testing paraffin embedded tissue samples from patients with myeloid sarcoma, order MSTF / Myeloid Sarcoma, FISH, Tissue.
Advise Express Mail or equivalent if not on courier service.
A reason for testing and a flow cytometry and/or a bone marrow pathology report (if available) should be submitted with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
Question ID | Description | Answers |
---|---|---|
GC059 | Reason for Referral | |
GC060 | Specimen |
Whole blood ACD Bone marrow ACD Whole blood Na Hep Bone marrow Na Hep Whole blood EDTA Bone marrow EDTA |
Submit only 1 of the following specimens:
Specimen Type: Bone marrow
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (heparin) or lavender top (EDTA)
Specimen Volume: 2 to 3 mL
Collection Instructions:
1. It is preferable to send the first aspirate from the bone marrow collection.
2. Invert several times to mix bone marrow.
3. Send bone marrow in original tube. Do not aliquot.
Specimen Type: Blood
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (heparin) or lavender top (EDTA)
Specimen Volume: 6 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood in original tube. Do not aliquot.
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Blood: 2 mL
Bone Marrow: 1 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Refrigerated |
Detecting a neoplastic clone associated with recurrent chromosome abnormalities seen in adult patients with acute myeloid leukemia (AML) or other myeloid malignancies
An adjunct to conventional chromosome studies in patients with AML
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
This test should not be used to screen for residual AML.
This test includes a charge for the probe application, analysis, and professional interpretation of results for 4 probe sets (8 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The initial panel includes testing for the following abnormalities using the probes listed:
-inv(16), [M4, Eos], MYH11/CBFB
-t(8;21), [M2], RUNX1T1/RUNX1
-t(15;17), [M3], PML/RARA
-11q23 rearrangement, [M0-M7], MLL (KMT2A)
Based on the results from the initial panel, if testing was ordered concurrently with a chromosomal study (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow or CHRHB / Chromosome Analysis, Hematologic Disorders, Blood), testing will be held pending the results of the chromosome test. If the chromosome results are complete and informative, only appropriate secondary FISH probes will be selected and performed. If testing was NOT ordered concurrently with a chromosomal study each of the secondary probes will be performed. The secondary panel includes testing for the following abnormalities using the probes listed:
-t(6;9), [M2,M4], DEK/NUP214
-inv(3) or t(3;3), [M1,2,4,6,7], RPN1/MECOM
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/D7S486
-17p-, TP53/D17Z1
-t(9;22), ABL1/BCR
When an MLL (KMT2A) rearrangement is identified, appropriate 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(AFDN)/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p12;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. In the event an 11q23 translocation is identified by conventional chromosome analysis, only the targeted MLL reflex probe will be performed if applicable.
In the absence of RPN1/MECOM fusion, when an extra RPN1 signal is identified, reflex testing using the PRDM16/RPN1 probe set will be considered at the laboratory’s discretion to identify a potential t(1;3)(p36;q21). Laboratory discretion may be influenced by available karyotype results.
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing may be performed at the laboratory’s discretion using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement. Laboratory discretion may be influenced by available karyotype results.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using the 5'RARA/3'RARA rearrangement probe set may be performed at the laboratory’s discretion to identify a potential variant translocation involving RARA. example: t(17;var)(q21;?). Laboratory discretion may be influenced by available karyotype results.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal is identified, reflex testing may be performed at the laboratory’s discretion using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement. Laboratory discretion may be influenced by available karyotype results.
The following algorithms are available:
Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
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 with associated clinical significance. 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 MLLT3- t(9;11), MLLT4)- t(6;11), MLLT10- t(10;11), and ELL- t(11;19p13.1).
Other recurrent chromosome abnormalities associated with AML include inv(3) or t(3;3), t(6;9) and t(9;22). In addition, AML can also evolve from myelodysplasia (MDS). Thus, the common chromosome abnormalities associated with MDS can also be identified in AML, which include: -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.
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.
The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.
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.
Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects many chromosome abnormalities associated with other hematological disorders that would be missed by this FISH panel test.
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 a hematopathologist).
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. Each probe set was evaluated to confirm the probe set detected the abnormality it was designed to detect.
2. 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 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196
This test is performed using commercially available and laboratory-developed probes. Deletion or monosomy of chromosomes 5, 7, and 17 are detected using enumeration strategy probes. Rearrangements involving ABL1, MLL (KMT2A), CBFB, and RARA are detected using a dual-color break-apart (BAP) strategy probe. Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe sets are used to detect inv(3), inv(16), t(8;21), t(15;17), t(6;9), t(8;16), t(3;21), t(1;3), t(1;22), t(9;22) and in reflex testing when rearrangements of the MLL gene are detected. For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. All results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
88271 x 8, 88275 x 4, 88291-FISH Probe, Analysis, Interpretation; 4 probe sets
88271 x 2, 88275 FISH Probe, Analysis; each additional probe set (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
AMLAF | Adult AML, FISH | In Process |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
609518 | Result Summary | 50397-9 |
609519 | Interpretation | 69965-2 |
609520 | Result Table | 93356-4 |
609521 | Result | 62356-1 |
GC059 | Reason for Referral | 42349-1 |
GC060 | Specimen | 31208-2 |
609522 | Source | 31208-2 |
609523 | Method | 85069-3 |
609524 | Additional Information | 48767-8 |
609525 | Disclaimer | 62364-5 |
609526 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
New Test | 2021-12-13 |