Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in pediatric/young adult patients with acute myeloid leukemia (AML)
An adjunct to conventional chromosome studies in patients with AML
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AMLPB | Probe, Each Additional (AMLPF) | No, (Bill Only) | No |
This test includes a charge for the probe application, analysis and professional interpretation of results for 13 probe sets (26 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The diagnostic pediatric/young adult FISH panel includes testing for the following abnormalities using the FISH 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)
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], KAT6A/CREBBP
t(1;22), [M7], RBM15/MKL1
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/ D7S486
12p13 rearrangement, ETV6
inv(16), GLIS2/CBFA2T3
11p15.4 rearrangement, NUP98
When an 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(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 absence of RPN1/MECOM fusion, when an extra MECOM signal is identified, reflex testing using the MECOM/RUNX1 probe set will be performed to identify a potential t(3;21)(q26.2;q22) rearrangement.
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 to identify a potential t(1;3)(p36;q21).
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing will be performed using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using a break-apart RARA probe set will be performed to identify a potential variant translocation involving RARA; example: t(17;var)( q21;?).
When an ETV6 rearrangement is identified, reflex testing using the MNX1/ETV6 probe set will be performed to identify a potential t(7;12)(q36;p13) rearrangement.
When a 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) rearrangement.
The following algorithms are available in Special Instructions:
Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
Fluorescence In Situ Hybridization (FISH)
-5 (monosomy 5)
-7 (monosomy 7)
NUP98 rearrangement
5q- (5q deletion)
7q- (7q deletion)
Acute Promyelocytic Leukemia (APL)
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;22)(p13.3;q13.1q13.2) - RBM15/MKL1
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(AFDN)/MLL or AF6/MLL
t(6;9)(p23;q34) - DEK/NUP214 or DEK/CAN
t(7;11)(p15;p15.4) - HOXA9/NUP98
t(8;16)(p11.2;p13.3) - KAT6A/CREBBP or MYST3/CREBBP
t(8;21)(q22;q22) - RUNX1T1/RUNX1 or ETO/AML1
t(9;11)(p22;q23) - MLLT3/MLL or AF9/MLL
inv(16)(p24.3;p13.3) - GLIS2/CBFA2T3
This test includes a charge for the probe application, analysis and professional interpretation of results for 13 probe sets (26 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The diagnostic pediatric/young adult FISH panel includes testing for the following abnormalities using the FISH 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)
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], KAT6A/CREBBP
t(1;22), [M7], RBM15/MKL1
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/ D7S486
12p13 rearrangement, ETV6
inv(16), GLIS2/CBFA2T3
11p15.4 rearrangement, NUP98
When an 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(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 absence of RPN1/MECOM fusion, when an extra MECOM signal is identified, reflex testing using the MECOM/RUNX1 probe set will be performed to identify a potential t(3;21)(q26.2;q22) rearrangement.
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 to identify a potential t(1;3)(p36;q21).
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing will be performed using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using a break-apart RARA probe set will be performed to identify a potential variant translocation involving RARA; example: t(17;var)( q21;?).
When an ETV6 rearrangement is identified, reflex testing using the MNX1/ETV6 probe set will be performed to identify a potential t(7;12)(q36;p13) rearrangement.
When a 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) rearrangement.
The following algorithms are available in Special Instructions:
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 30 years of age or younger.
This test is intended for instances when the entire AML fluorescence in situ hybridization (FISH) panel is needed for a pediatric patient.
-If this test is ordered on a patient older than 30 years, this test will be canceled and automatically reordered by the laboratory as AMLAF / Acute Myeloid Leukemia, FISH, Adult, 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.
If limited AML FISH probes are preferred, order AMLMF / Acute Myeloid Leukemia, Specified FISH, Varies.
At follow-up, targeted AML FISH probes can be evaluated based on the specific abnormalities identified in the diagnostic study. Order AMLMF / Acute Myeloid Leukemia (AML), Specified FISH, Varies 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.
1. 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.
2. If the patient has received an opposite sex bone marrow transplant prior to specimen collection for this protocol, note this information on the request.
Already noted above as optional. If required will need to reword above statement.
Question ID | Description | Answers |
---|---|---|
GC062 | Reason for Referral | |
GC063 | 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:
Preferred
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.
Acceptable
Specimen Type: Blood
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (heparin) or lavender top (EDTA)
Specimen Volume: 6 mL
Collection Instructions: Invert several times to mix blood.
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 the common chromosome abnormalities and classic rearrangements seen in pediatric/young adult patients with acute myeloid leukemia (AML)
An adjunct to conventional chromosome studies in patients with AML
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
This test includes a charge for the probe application, analysis and professional interpretation of results for 13 probe sets (26 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The diagnostic pediatric/young adult FISH panel includes testing for the following abnormalities using the FISH 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)
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], KAT6A/CREBBP
t(1;22), [M7], RBM15/MKL1
-5/5q-, D5S630/EGR1
-7/7q-, D7Z1/ D7S486
12p13 rearrangement, ETV6
inv(16), GLIS2/CBFA2T3
11p15.4 rearrangement, NUP98
When an 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(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 absence of RPN1/MECOM fusion, when an extra MECOM signal is identified, reflex testing using the MECOM/RUNX1 probe set will be performed to identify a potential t(3;21)(q26.2;q22) rearrangement.
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 to identify a potential t(1;3)(p36;q21).
In the absence of MYH11/CBFB fusion, when an extra CBFB signal is identified, reflex testing will be performed using the CBFB break-apart probe set to evaluate for the presence or absence of an CBFB rearrangement.
In the absence of PML/RARA fusion, when an extra or atypical RARA signal is identified, testing using a break-apart RARA probe set will be performed to identify a potential variant translocation involving RARA; example: t(17;var)( q21;?).
When an ETV6 rearrangement is identified, reflex testing using the MNX1/ETV6 probe set will be performed to identify a potential t(7;12)(q36;p13) rearrangement.
When a 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) rearrangement.
The following algorithms are available in Special Instructions:
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. 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(MLLT4)- 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-. 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 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.
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: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017
This test is performed using commercially available and laboratory-developed probes. Deletion or monosomy of chromosomes 5 and 7 are detected using enumeration strategy probes. Rearrangements involving MLL (KMT2A), NUP98, ETV6, 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(7;11), t(7;12), 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.
88271x26, 88275x13, 88291 x1-FISH Probe, Analysis, Interpretation; 13 probe sets
88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
AMLPF | Pediatric 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.
|
---|---|---|
609528 | Result Summary | 50397-9 |
609529 | Interpretation | 69965-2 |
609530 | Result Table | 93356-4 |
609531 | Result | 62356-1 |
GC062 | Reason for Referral | 42349-1 |
GC063 | Specimen | 31208-2 |
609532 | Source | 31208-2 |
609533 | Method | 85069-3 |
609534 | Additional Information | 48767-8 |
609535 | Disclaimer | 62364-5 |
609536 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
New Test | 2021-12-13 |