Test Id : CILMF

This test includes a charge for the probe application, analysis, and professional interpretation of results for 1 probe set (2 individual fluorescence in situ hybridization probes). Additional charges will be incurred for all reflex or additional probe sets performed.

If the patient is being treated for known abnormalities, indicate the abnormality and which probes should be used.

When specified, any of the following primary or reflex probes will be performed; reflex probes are noted with an asterisk*: Reflex probes can be added, as requested, but remain optional.

11q23 rearrangement, MLL (KMT2A)

*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;19)(q23;p13.1) MLL/ELL

*t(11;19)(q23;p13.3) MLL/MLLT1

t(8;16), KAT6A/CREBBP

*D8Z2/MYC for trisomy 8

t(1;22), RBM15/MKL1

+13/+21, 13q14 and 21q22

inv(16), MYH11/CBFB

*16q22 rearrangement, CBFB break-apart

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

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

*17q21 rearrangement, RARA break-apart

-5/5q-, D5S630/EGR1

-7/7q-, D7Z1/ D7S486

inv(3) or t(3;3), RPN1/MECOM

*3q26.2 rearrangement, MECOM break-apart

t(6;9), DEK/NUP214

12p13 rearrangement, ETV6 break-apart

*t(7;12)(q36;p13), MNX1/ETV6

inv(16), GLIS2/CBFA2T3

11p15.4 rearrangement, NUP98 break-apart

*t(7;11)(p15;p15.4), HOXA9/NUP98

+9/9p-, CDKN2A/D9Z1

t(9;22) BCR/ABL1, ABL1 amplification

*9q34 rearrangement, ABL1 break-apart

-17/17p-, TP53/D17Z1

t(1;19)(q23;p13), PBX1/TCF3

Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1

t(12;21)(p13;q22), ETV6/RUNX1 fusion, iAMP21

*12p13 rearrangement, ETV6 break-apart

14q32 rearrangement, IGH break-apart

t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement

*t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32), CRLF2/IGH

t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement

8q24.1 rearrangement, MYC break-apart

1q25 rearrangement, ABL2 break-apart

5q32 rearrangement, PDGFRB break-apart

9p24.1 rearrangement, JAK2 break-apart

9q34 rearrangement, ABL1 break-apart

7p-, IKZF1/CEP7

t(5;14), TLX3/BCL11B

7q34 rearrangement, TRB break-apart

*t(6;7) - MYB/TRB fusion

*t(7;10) - TRB/TLX1

*t(7;11) - TRB/LMO1

*t(7;11) - TRB/LMO2

14q11.2 rearrangement, TRAD break-apart

*t(8;14) - MYB/TRAD

*t(10;14) - TLX1/TRAD

*t(11;14) - LMO1/TRAD

*t(11;14) - LMO2/TRAD

t(10;11), MLLT10/PICALM

1p33 rearrangement, TAL1/STIL

This test is only performed on specimens from patients with acute leukemia who are 18 months of age or younger.

This test is intended for instances when limited congenital infantile leukemia fluorescence in situ hybridization (FISH) probes are needed. The FISH probes to be analyzed must be specified on the request, otherwise test processing may be delayed in order to determine the intended analysis.

-If specific probes are not included with this order, the test may be canceled and automatically reordered by the laboratory as CILDF / Congenital Infantile Leukemia, Diagnostic FISH, Varies.

-If this test is ordered on a patient 19 months or older, this test will be canceled and automatically reordered by the laboratory as BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies ; TALPF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies; or AMLPF / Acute Myeloid Leukemia (AML), FISH, Pediatric, Varies, based on patient's reason for testing.

-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 COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies; COGTF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies; or COGMF / Acute Myeloid Leukemia (AML), Children's Oncology Group Enrollment Testing, FISH, Varies based on the patient's protocol.

If the entire congenital infantile leukemia FISH panel is preferred, order CILDF / Congenital Infantile Leukemia, Diagnostic FISH, Varies.

At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and a complete CILDF / Congenital Infantile Leukemia, Diagnostic FISH, Varies panel should be performed.

For testing paraffin embedded tissue samples from patients with congenital infantile leukemia, order CILPF / Congenital Infantile Leukemia, FISH, Tissue.

Advise Express Mail or equivalent if not on courier service.

1. A list of probes requested for analysis is required. Probes available for this test are listed in the Testing Algorithm section.

2. 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; however, appropriate testing and interpretation may be compromised or delayed. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

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: 2-3 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 specimen in original tube. Do not aliquot.

Acceptable

Specimen Type: Whole 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 specimen 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

Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in infant patients with leukemia using client specified probe sets

An adjunct to conventional chromosome studies in infant patients with leukemia.

This test includes a charge for the probe application, analysis, and professional interpretation of results for 1 probe set (2 individual fluorescence in situ hybridization probes). Additional charges will be incurred for all reflex or additional probe sets performed.

If the patient is being treated for known abnormalities, indicate the abnormality and which probes should be used.

When specified, any of the following primary or reflex probes will be performed; reflex probes are noted with an asterisk*: Reflex probes can be added, as requested, but remain optional.

11q23 rearrangement, MLL (KMT2A)

*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;19)(q23;p13.1) MLL/ELL

*t(11;19)(q23;p13.3) MLL/MLLT1

t(8;16), KAT6A/CREBBP

*D8Z2/MYC for trisomy 8

t(1;22), RBM15/MKL1

+13/+21, 13q14 and 21q22

inv(16), MYH11/CBFB

*16q22 rearrangement, CBFB break-apart

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

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

*17q21 rearrangement, RARA break-apart

-5/5q-, D5S630/EGR1

-7/7q-, D7Z1/ D7S486

inv(3) or t(3;3), RPN1/MECOM

*3q26.2 rearrangement, MECOM break-apart

t(6;9), DEK/NUP214

12p13 rearrangement, ETV6 break-apart

*t(7;12)(q36;p13), MNX1/ETV6

inv(16), GLIS2/CBFA2T3

11p15.4 rearrangement, NUP98 break-apart

*t(7;11)(p15;p15.4), HOXA9/NUP98

+9/9p-, CDKN2A/D9Z1

t(9;22) BCR/ABL1, ABL1 amplification

*9q34 rearrangement, ABL1 break-apart

-17/17p-, TP53/D17Z1

t(1;19)(q23;p13), PBX1/TCF3

Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1

t(12;21)(p13;q22), ETV6/RUNX1 fusion, iAMP21

*12p13 rearrangement, ETV6 break-apart

14q32 rearrangement, IGH break-apart

t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement

*t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32), CRLF2/IGH

t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement

8q24.1 rearrangement, MYC break-apart

1q25 rearrangement, ABL2 break-apart

5q32 rearrangement, PDGFRB break-apart

9p24.1 rearrangement, JAK2 break-apart

9q34 rearrangement, ABL1 break-apart

7p-, IKZF1/CEP7

t(5;14), TLX3/BCL11B

7q34 rearrangement, TRB break-apart

*t(6;7) - MYB/TRB fusion

*t(7;10) - TRB/TLX1

*t(7;11) - TRB/LMO1

*t(7;11) - TRB/LMO2

14q11.2 rearrangement, TRAD break-apart

*t(8;14) - MYB/TRAD

*t(10;14) - TLX1/TRAD

*t(11;14) - LMO1/TRAD

*t(11;14) - LMO2/TRAD

t(10;11), MLLT10/PICALM

1p33 rearrangement, TAL1/STIL

While pediatric leukemia is the most common malignancy affecting children, acute leukemia occurring prior to the age of 18 months (infant leukemia) or occurring within the first 3 months of life (congenital leukemia) is relatively rare in occurrence. The incidence of congenital and infant acute leukemia cases (through 12 months of age) is estimated at only 30 to 40 cases/million/year, with the majority comprising infant cases. Nearly all cases of congenital and infant acute leukemia represent either acute myeloid leukemia (AML) or B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) with only very rare cases of T-cell acute lymphoblastic leukemia/lymphoma identified in this age group.

Characteristic genetic abnormalities have been identified in both the congenital acute leukemia and infant acute leukemia setting, each with uniquely associated clinical-pathologic correlations. Rare but important patients with KAT6A/CREBBP translocations and congenital acute leukemia have been described with spontaneously remitting AML despite the lack of therapeutic intervention. In addition, transient abnormal myelopoiesis associated with Down syndrome is another common manifestation encountered in the neonatal setting that can be associated with the development of infant acute leukemia. In contrast, nearly 80% of infant acute leukemia cases are associated with MLL(KMT2A) translocation events with varying percentages of translocation partners based on an AML versus B-ALL/LBL presentation.

Due to the underlying genetic heterogeneity associated with both congenital and infant leukemia and the important prognostic, diagnostic and occasional therapeutic targets identified, appropriate genetic characterization of this uncommon acute leukemia presentation is critical. These thorough fluorescence in situ hybridization (FISH) panels have been developed by Mayo Clinic Laboratories to interrogate the more common AML and B-ALL abnormalities associated with both congenital and infant acute leukemias. These FISH probes have been validated both in bone marrow/blood (CILDF / Congenital Infantile Leukemia, Diagnostic FISH, Varies) and in paraffin (CILPF / Congenital Infantile Leukemia, FISH, Tissue), since a significant minority of these patients present clinically with isolated extramedullary (tissue) manifestations (ie, myeloid sarcoma).

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 clinical and pathologic information.

Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects chromosome abnormalities associated with other hematological disorders that would be missed by this FISH panel test.

Bone marrow is the preferred sample type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are neoplastic 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. Swerdlow SH, Campo E, Harris NL, et al, eds: WHO Classification of Tumours. Vol 2. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2017

2. Tomizawa D: Recent progress in the treatment of infant acute lymphoblastic leukemia. Pediatr Int. 2015;57(5):811-819. doi: 10.1111/ped.12758

3. Inaba H, Zhou Y, Abla O, et al: Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood. 2015;126(13):1575-84. doi: 10.1182/blood-2015-02-629204

4. Coenen EA, Zwaan CM, Reinhardt D, et al: Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group. Blood. 2013;122(15):2704-13. doi: 10.1182/blood-2013-02-485524

This test is performed using commercially available and laboratory-developed probes. Gain or loss of chromosomes 4, 5, 7, 8, 13, 17, and 21 are detected using enumeration strategy probes. Deletion of the CDKN2A locus on chromosome 9, TP53 on chromosome 17, and deletion of IKZF1 on chromosome 7 are detected using an enumeration strategy.

Rearrangements involving the following genes: MLL (KMT2A), NUP98, ETV6, CBFB, RARA, ABL2, PDGFRB, MYC, JAK2, ABL1, IGH, CRLF2, P2RY8, TAL1/STIL, TRB, and TRAD are detected using a dual-color break-apart (BAP) strategy probe. If a MYC gene region separation is identified, break-apart BCL2 and BCL6 will be evaluated 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), t(9;22), t(12;21), t(1;19), t(5;14), t(9;22), t(10;11), and in reflex testing when a rearrangement of the MLL, TRB, TRAD gene region is observed. Amplification of ABL1 (9q34) or RUNX1 (iAMP21; 21q22) is detected using a D-FISH probe strategy. 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

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• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 x2, 88275 x1, 88291 x1-FISH Probe, Analysis, Interpretation; 1 probe set

88271 x2, 88275 x1-FISH Probe, Analysis; each additional probe set (if appropriate)