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*
*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.
1. Provide a reason for referral 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.
2. A pathology and/or flow cytometry report may be requested by the Genomics Laboratory to optimize testing and aid in interpretation of results.
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.
An interpretive report will be provided.