As an adjunct to conventional chromosome studies for pediatric patients with B-ALL and Ph-like ALL
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
BALPB | Probe, Each Additional (BALPF) | No, (Bill Only) | No |
This test includes a charge for the probe application, analysis, and professional interpretation of results for 11 probe sets (23 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
The standard (diagnostic) pediatric/young adult B-cell acute lymphoblastic leukemia (B-ALL) FISH panel includes testing for the following abnormalities using the FISH probes listed:
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
11q23 rearrangement, MLL (KMT2A) 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
14q32 rearrangement, IGH break-apart
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
8q24.1 rearrangement, MYC break-apart
If the standard (diagnostic) pediatric/young adult B-ALL FISH panel demonstrates normal or nonclassical abnormalities, the Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel will be performed.
The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below, as well as IKZF1 deletion, which often accompanies Ph-like ALL:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
7p-, IKZF1/CEP7
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;19)(q23;p13.1) MLL/ELL
t(11;19)(q23;p13.3) MLL/MLLT1
When an IGH and/or CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal 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.
In the absence of ETV6/RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing will be performed using the ETV6 break-apart probe set to evaluate for the presence or absence of an ETV6 rearrangement.
If a MYC rearrangement is identified, both the BCL2 and BCL6 probe sets will be performed.
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Fluorescence In Situ Hybridization (FISH)
+4,+10,+17
17p- (17p deletion) or TP53
9p- (9p deletion) or CDKN2A or p16
ABL1 (9q34) rearrangement
ABL2 (1q25) rearrangement
BCR-ABL1 like ALL
CRLF2 (Xp22.33) or (Yp11.32) rearrangement
Hyperdiploidy
Hypodiploid/pseudo-hyperdiploid
Hypotriploid/Near-Triploid
iAMP21
IGH (14q32) rearrangement
IKZF1 deletion
JAK2 (9p24.1) rearrangement
MLL or KMT2A (11q23) rearrangement
P2RY8 (Xp22.33) or (Yp11.32) rearrangement
Ph-like ALL
Philadelphia-like ALL
t(1;19)(q23;p13.3) - PBX1/TCF3
t(10;11)(p12;q23) - MLLT10/MLL or AF10/MLL
t(11;19)(q23;p13.1) - MLL/ELL
t(11;19)(q23;p13.3) - MLL/MLLT1 or MLL/ENL
t(12;21)(p13;q22) - TEL/AML1 or ETV6/RUNX1
t(4;11)(q21;q23) - AFF1/MLL or AF4/MLL
t(6;11)(q27;q23) - MLLT4(AFDN)/MLL or AF6/MLL
t(9;11)(p22;q23) - MLLT3/MLL or AF9/MLL
t(9;22)(9q34;q11.2) - BCR/ABL1
t(X;14)(p22.3;q32) - CRLF2/IGH
t(Y;14)(p11.32;q32) - CRLF2/IGH
MYC (8q24.1) rearrangement
12p13 rearrangement, ETV6
PDGFRB (5q23) rearrangement
This test includes a charge for the probe application, analysis, and professional interpretation of results for 11 probe sets (23 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
The standard (diagnostic) pediatric/young adult B-cell acute lymphoblastic leukemia (B-ALL) FISH panel includes testing for the following abnormalities using the FISH probes listed:
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
11q23 rearrangement, MLL (KMT2A) 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
14q32 rearrangement, IGH break-apart
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
8q24.1 rearrangement, MYC break-apart
If the standard (diagnostic) pediatric/young adult B-ALL FISH panel demonstrates normal or nonclassical abnormalities, the Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel will be performed.
The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below, as well as IKZF1 deletion, which often accompanies Ph-like ALL:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
7p-, IKZF1/CEP7
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;19)(q23;p13.1) MLL/ELL
t(11;19)(q23;p13.3) MLL/MLLT1
When an IGH and/or CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal 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.
In the absence of ETV6/RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing will be performed using the ETV6 break-apart probe set to evaluate for the presence or absence of an ETV6 rearrangement.
If a MYC rearrangement is identified, both the BCL2 and BCL6 probe sets will be performed.
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Varies
This test is only performed on specimens from patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) who are 30 years of age or younger.
This test is intended to be ordered when the entire B-ALL fluorescence in situ hybridization (FISH) panel is needed for a pediatric patient.
-If this test is ordered on a patient 31 years of age or older, this test will be canceled and automatically reordered by the laboratory as BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Adult, FISH, 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 COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies.
If PHLDF / Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (Ph-like ALL), Diagnostic FISH, Varies is ordered concurrently with this test, PHLDF testing will be canceled. The probes offered in PHLDF are included within this test, when appropriate.
If limited B-cell ALL FISH probes are preferred, order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies.
At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted B-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study. Order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies and request specific probes or abnormalities.
If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.
For testing paraffin-embedded tissue samples from patients with B-cell acute lymphoblastic lymphoma, order BLBLF / B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, it will be canceled and BLBLF will be added and performed as the appropriate test.
At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and this test should be performed. If there is limited specimen available, this test only will be performed.
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 should be submitted with each specimen. The laboratory will not reject testing if this information is not provided; however, appropriate testing and/or interpretation may be compromised or delayed in some instances. If 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, note this information on the request.
Question ID | Description | Answers |
---|---|---|
GC068 | Reason for Referral | |
GC069 | 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: 2-3 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
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Refrigerated |
As an adjunct to conventional chromosome studies for pediatric patients with B-ALL and Ph-like ALL
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 11 probe sets (23 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.
If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
The standard (diagnostic) pediatric/young adult B-cell acute lymphoblastic leukemia (B-ALL) FISH panel includes testing for the following abnormalities using the FISH probes listed:
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
11q23 rearrangement, MLL (KMT2A) 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
14q32 rearrangement, IGH break-apart
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
8q24.1 rearrangement, MYC break-apart
If the standard (diagnostic) pediatric/young adult B-ALL FISH panel demonstrates normal or nonclassical abnormalities, the Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel will be performed.
The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below, as well as IKZF1 deletion, which often accompanies Ph-like ALL:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
7p-, IKZF1/CEP7
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;19)(q23;p13.1) MLL/ELL
t(11;19)(q23;p13.3) MLL/MLLT1
When an IGH and/or CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal 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.
In the absence of ETV6/RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing will be performed using the ETV6 break-apart probe set to evaluate for the presence or absence of an ETV6 rearrangement.
If a MYC rearrangement is identified, both the BCL2 and BCL6 probe sets will be performed.
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
A newly recognized World Health Organization entity BCR-ABL1-like ALL, also known as Philadelphia chromosome-like acute lymphoblastic leukemia, is increasing in importance due to the poor prognosis seen in pediatric, adolescent, and young adult ALL. Common features of this entity involve rearrangements with tyrosine kinase genes involving the following genes: ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8. Deletion of IKZF1 often accompanies this entity. Some patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies in clinical trials when rearrangements involving these specific gene regions have been identified.
Evaluation of the MYC gene region is included in all diagnostic B-ALL panels to evaluate for Burkitt lymphoma. If a positive result is obtained, additional testing for the BCL2 and BCL6 gene regions will be performed.
Additional cytogenetic techniques such as chromosomal microarray (CMAH / Chromosomal Microarray, Hematologic Disorders, Varies) may be helpful to resolve questions related to ploidy (hyperdiploid clone vs doubled hypodiploid clone) or to resolve certain clonal structural rearrangements such as the presence or absence of intra-chromosomal amplification of chromosome 21 (iAMP21). A summary of the characteristic chromosome abnormalities identified in B-ALL is listed in the following table.
Table. Common Chromosome Abnormalities in B-cell Acute Lymphoblastic Leukemia
Cytogenetic change | Typical demographic | Risk category | |
B-acute lymphoblastic leukemia | t(12;21)(p13;q22), ETV6/RUNX1 | Pediatric | Favorable |
Hyperdiploidy | Pediatric | Favorable | |
t(1;19)(q23;p13.3), PBX1/TCF3 | Pediatric | Intermediate to favorable | |
t(9;22)(q34;q11.2), BCR/ABL1 | All ages | Unfavorable | |
iAMP21, RUNX1 | Pediatric | Unfavorable | |
del(9p), CDKN2A | All ages | Unknown | |
t(11q23;var), MLL | All ages | Unfavorable | |
t(4;11)(q21;q23), AFF1/MLL | All ages | Unfavorable | |
t(6;11)(q27;q23), MLLT4(AFDN)/MLL | All ages | Unfavorable | |
t(9;11)(p22;q23), MLLT3/MLL | All ages | Unfavorable | |
t(10;11)(p12;q23), MLLT10/MLL | All ages | Unfavorable | |
t(11;19)(q23;p13.1), MLL/ELL | All ages | Unfavorable | |
t(11;19)(q23;p13.3), MLL/MLLT1 | All ages | Unfavorable | |
t(14q32;var), IGH | All ages | Variable | |
t(X;14)(p22;q32)/t(Y;14)(p11;q32), CRLF2/IGH | Adolescent/ young adult | Unfavorable | |
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 | All ages | Unfavorable | |
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 | All ages | Unfavorable | |
-17/17p-, TP53 | All ages | Unfavorable | |
t(8q24.1;var), MYC *representing Burkitt or other mature B-cell lymphoma | Pediatric/ adolescent/ young adult | ||
Complex karyotype (> or =4 abnormalities) | Adult | Unfavorable | |
Low hypodiploidy/near triploidy | Adult | Unfavorable | |
Near-haploid/hypodiploid | All ages | Unfavorable | |
del(7p) IKZF1 | All ages | Unfavorable in absence of ERG deletion | |
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) | t(1q25;var), ABL2 | Pediatric/ adolescent/ young adult | Unfavorable |
t(5q32;var), PDGFRB | |||
t(9p24.1;var), JAK2 | |||
t(9q34;var), ABL1 | |||
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 | |||
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 |
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.
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 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).
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. Moorman AV, Harrison CJ, Buck GA, et al: Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007 Apr 15;109(8):3189-3197
2. Moorman AV: The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev. 2012;26:123-135
3. Roberts KG, Li Y, Payne-Turner D, et al: Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014 Sept;371(11):1005-1015
4. Mullighan CG: The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-180
This test is performed using commercially available and laboratory-developed probes. Deletion of the CDKN2A locus on chromosome 9, TP53 on chromosome 17, deletion of IKZF1 on chromosome 7, and gain of chromosomes 4, 10, and 17 are detected using enumeration strategy probes. Rearrangements involving ABL2, PDGFRB, MYC, JAK2, ABL1, MLL, ETV6, IGH, MYC, CRLF2 and P2RY8 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 t(X/Y;14), t(9;22), t(12;21), t(1;19), and in reflex testing when rearrangements of the MLL gene is detected. If a MYC gene region separation is identified, break-apart BCL2 and BCL6 will be evaluated using a dual-color BAP strategy probe. For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. 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 23
88271 x 2
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
BALPF | Pediatric ALL (B-cell), 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.
|
---|---|---|
609548 | Result Summary | 50397-9 |
609549 | Interpretation | 69965-2 |
609550 | Result Table | 93356-4 |
609551 | Result | 62356-1 |
GC068 | Reason for Referral | 42349-1 |
GC069 | Specimen | 31208-2 |
609552 | Source | 31208-2 |
609553 | Method | 85069-3 |
609554 | Additional Information | 48767-8 |
609555 | Disclaimer | 62364-5 |
609556 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
New Test | 2021-12-13 |