Testing Algorithm

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)

If testing was ordered concurrently with a chromosomal study (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow or CHRHB / Chromosome Analysis, Hematologic Disorders, Blood), secondary testing will not be performed. Appropriate secondary FISH probes will be recommended if the chromosome results are informative.

Based on the results from the initial panel, the following secondary panel of FISH probes will be performed, when appropriate, if testing was NOT ordered concurrently with a chromosomal study.

-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 and RUNX1/RUNX1T1 fusion, when an extra MECOM signal and an extra RUNX1 signal are identified, reflex testing using the MECOM/RUNX1 probe set will be considered at the laboratory's discretion to identify a potential t(3;21)(q26.2;q22) rearrangement. Laboratory discretion may be influenced by available karyotype results.

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 Leukemias of Ambiguous Lineage Testing Algorithm

Acute Myeloid Leukemia: Testing Algorithm