STEPTRACKERHEMATOLOGY + ONCOLOGY | PATHOLOGY + GENETICS | HIGH-YIELD REVIEW

Translocations & Markers in Heme-Onc

The chapter's genetic and immunophenotype hooks in one place — use it as the last pass before a block.

FOCUS ON
Most B-cell lymphoma translocations move an oncogene next to the IGH enhancer on chromosome 14, which overexpresses it (MYC, BCL2, cyclin D1). Leukemia translocations usually make a fusion protein (BCR-ABL, PML-RARA). Pair each with its disease and drug.
ABNORMALITY
GENES
DISEASE
NOTE
t(9;22)
Philadelphia
BCR-ABL fusion tyrosine kinase
CML; Ph⁺ ALL
Imatinib; poor prognosis in ALL
t(15;17)
PML-RARA
Acute promyelocytic leukemia
DIC; ATRA + arsenic
t(8;14)
MYC → IGH
Burkitt lymphoma
Also t(8;22), t(2;8) with light-chain loci
t(14;18)
IGH → BCL2
Follicular lymphoma; some DLBCL
Blocks apoptosis
t(11;14)
CCND1 (cyclin D1) → IGH
Mantle cell lymphoma
CD5⁺ CD23⁻
t(11;18)
API2-MALT1
MALT lymphoma
Won't regress with H pylori therapy
t(12;21)
ETV6-RUNX1
Childhood B-ALL
Good prognosis
t(8;21) · inv(16)
RUNX1-RUNX1T1 · CBFB-MYH11
AML (inv(16) with abnormal eosinophils)
Both favorable
KMT2A (MLL) rearrangement
e.g., t(4;11)
Infant ALL; some AML
Poor prognosis
t(2;5)
NPM-ALK
Anaplastic large cell lymphoma
CD30⁺; better prognosis
Point mutations
JAK2 V617F · BRAF V600E · MYD88 L265P · KIT D816V
PV/ET/PMF · hairy cell, LCH · Waldenström · mastocytosis
CALR, MPL in ET/PMF
Prognostic markers
FLT3-ITD · NPM1 · SF3B1 · del(5q) · del(17p)/TP53 · del(13q)
AML poor · AML good · MDS ring sideroblasts · MDS (lenalidomide) · CLL poor · CLL good
TP53 loss = poor almost everywhere

Mechanism — two ways a translocation causes cancer

Oncogene movesNext to IGH (chr 14)
→
OverexpressionMYC, BCL2, cyclin D1
→
B-cell lymphoma
Two genes fuseBCR + ABL, PML + RARA
→
New proteinKinase on, or maturation blocked
→
LeukemiaTargetable

CD marker quick sheet

MARKER
MARKS
CD34 · TdT
Stem cells/blasts · lymphoblasts
MPO, CD13, CD33, CD117
Myeloid blasts (CD117 also mast cells, GIST)
CD19, CD20, CD22, CD79a
B cells
CD2, CD3, CD5, CD7
T cells (CD5 also CLL, mantle cell)
CD10
Germinal center (follicular, Burkitt), B-ALL
CD23
CLL (vs mantle cell)
CD11c, CD25, CD103
Hairy cell leukemia
CD15, CD30
Reed-Sternberg cells; CD30 also ALCL
CD1a, S-100, CD207
Langerhans cell histiocytosis
CD138
Plasma cells
CD41, CD61
Megakaryoblasts (AML-M7)
CD56
NK cells

How it's tested

COMMON CONFUSIONt(11;14) is mantle cell, t(11;18) is MALT, and t(14;18) is follicular. Use the shared "14 = IGH" to anchor them.
THE TRAPA question names only the karyotype and asks for the treatment. t(9;22) → TKI; t(15;17) → ATRA/arsenic; KIT D816V → imatinib-resistant KIT inhibitor.
YOUR APPROACHKaryotype → gene → disease → prognosis → drug. Then confirm with the matching CD markers.

If you see… think…

Chromosome 14 + 18 → BCL2 → follicular lymphoma
Chromosome 8 + 14 → MYC → Burkitt lymphoma
Chromosome 11 + 14 → cyclin D1 → mantle cell
Chromosome 11 + 18 → MALT1 → MALT lymphoma
Chromosome 9 + 22 → BCR-ABL → CML
Chromosome 15 + 17 → PML-RARA → APL
Chromosome 12 + 21 in a child → good-prognosis B-ALL
Chromosome 2 + 5 with CD30 → ALCL
BRAF V600E in a hematologic disease → hairy cell leukemia or LCH
MYD88 L265P with IgM → Waldenström