Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) using client specified probes
An adjunct to conventional chromosome studies for patients with B-ALL/LBL
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
BALMB | Probe, Each Additional (BALMF) | No, (Bill Only) | No |
BAL3B | Probe, Tri-color (BAL) | No, (Bill Only) | No |
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 [FISH] probes or 3 individual FISH 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 probes will be performed:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
7p-, IKZF1/CEP7
9p24.1 rearrangement, JAK2 break-apart
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
9q34 rearrangement, ABL1 break-apart
11q23 rearrangement, MLL (KMT2A) break-apart
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)(p13;q23), MLLT10/MLL
t(11;19)(q23;p13.1), MLL/ELL
t(11;19)(q23;p13.3), MLL/MLLT1
-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 & iAMP21
12p13 rearrangement, ETV6 break-apart
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
t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) ), CRLF2/IGH
8q24.1 rearrangement, MYC break-apart
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 (5q32) rearrangement
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 [FISH] probes or 3 individual FISH 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 probes will be performed:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
7p-, IKZF1/CEP7
9p24.1 rearrangement, JAK2 break-apart
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
9q34 rearrangement, ABL1 break-apart
11q23 rearrangement, MLL (KMT2A) break-apart
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)(p13;q23), MLLT10/MLL
t(11;19)(q23;p13.1), MLL/ELL
t(11;19)(q23;p13.3), MLL/MLLT1
-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 & iAMP21
12p13 rearrangement, ETV6 break-apart
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
t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) ), CRLF2/IGH
8q24.1 rearrangement, MYC break-apart
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Varies
This test is intended for instances when targeted B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) fluorescence in situ hybridization (FISH) probes are needed based on specific abnormalities or abnormalities identified in the diagnostic sample. 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 test request, the test may be canceled and automatically reordered by the laboratory as BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies depending on the age of the patient.
-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 COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies.
For an adult patient, if the entire B-cell ALL FISH panel is preferred, order BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies.
For a pediatric patient, if the entire B-cell ALL FISH panel is preferred, order BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies.
At diagnosis, both conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies should be performed.
If the patient clinically relapses, a conventional chromosome study may be useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a therapy-related myeloid clone.
For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.
Advise Express Mail or equivalent if not on courier service.
2. 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.
Question ID | Description | Answers |
---|---|---|
GC101 | Reason for Referral | |
GC102 | Probes Requested | |
GC103 | 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:
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.
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 |
Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) using client specified probes
An adjunct to conventional chromosome studies for patients with B-ALL/LBL
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 1 probe set (2 individual fluorescence in situ hybridization [FISH] probes or 3 individual FISH 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 probes will be performed:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
7p-, IKZF1/CEP7
9p24.1 rearrangement, JAK2 break-apart
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
9q34 rearrangement, ABL1 break-apart
11q23 rearrangement, MLL (KMT2A) break-apart
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)(p13;q23), MLLT10/MLL
t(11;19)(q23;p13.1), MLL/ELL
t(11;19)(q23;p13.3), MLL/MLLT1
-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 & iAMP21
12p13 rearrangement, ETV6 break-apart
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
t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) ), CRLF2/IGH
8q24.1 rearrangement, MYC break-apart
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
In the United States, the incidence of B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is roughly 6000 new cases per year, or approximately 1 in 50,000. B-ALL/LBL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. It has a peak incidence at 2 to 5 years of age. This incidence decreases with age before increasing again at around 50 years of age. B-ALL/LBL is slightly more common in male patients than female patients. There is also an increased incidence of B-ALL/LBL in individuals with genetic conditions such as Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for B-ALL/LBL in children is approximately 90%, and about 45% to 60% of adults have long-term disease-free survival. Of note, CRLF2/IGH rearrangements are more commonly observed in patients with Down syndrome or of Hispanic descent.
Specific cytogenetic abnormalities are identified in the majority of cases of B-ALL/LBL, either by conventional chromosome studies or fluorescence in situ hybridization (FISH) studies. Each of the genetic subgroups is important to detect and can be critical prognostic markers. For example, a decision for early transplantation may be made if t(9;22)(q34;q11.2), KMT2A rearrangement, iAMP21, or a hypodiploid clone is identified. In contrast, if the ETV6/RUNX1 fusion or hyperdiploidy is identified, the patient has a more favorable prognosis and transplantation is rarely initially considered.
A newly recognized World Health Organization entity called 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, as well as deletions involving IKZF1. Patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies 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 may be considered.
Per National Comprehensive Cancer Network guidelines, a combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients with B-ALL/ lymphoblastic lymphoma.
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.
Bone marrow is the preferred specimen type for this fluorescence in situ hybridization 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. 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. doi: 10.1182/blood-2006-10-051912
2. Moorman AV: The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev. 2012;26:123-135. doi: 10.1016/j.blre.2012.01.001
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. i: 10.1056/NEJMoa1403088
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. doi: 10.1182/asheducation-2014.1.174
5. Arber DA, Orazi A, Hasserjian R, et al: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-2405. doi: 10.1182/blood-2016-03-643544
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. Amplification of RUNX1 (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. 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 x2, 88275 x1, 88291 x1- FISH Probe, Analysis, Interpretation; 1 probe sets
88271 x2, 88275 x1 - FISH Probe, Analysis; each additional probe set (if appropriate)
88271 x1 –-FISH Probe; coverage for sets containing 3 probes (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
BALMF | ALL (B-cell), Specified 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.
|
---|---|---|
614217 | Result Summary | 50397-9 |
614218 | Interpretation | 69965-2 |
614219 | Result Table | 93356-4 |
614220 | Result | 62356-1 |
GC101 | Reason for Referral | 42349-1 |
GC102 | Probes Requested | 78040-3 |
GC103 | Specimen | 31208-2 |
614221 | Source | 31208-2 |
614222 | Method | 85069-3 |
614223 | Additional Information | 48767-8 |
614224 | Disclaimer | 62364-5 |
614225 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
New Test | 2021-12-13 |